1
|
Najafi E, Pourfarzi F, Mazani M, Yazdanbod A, Rezagholizadeh K, Fazaeli A. Paraoxonase 1 polymorphisms and their relationship with gastric cancer risk: a biochemical perspective on oxidative stress. Mol Biol Rep 2025; 52:472. [PMID: 40397201 DOI: 10.1007/s11033-025-10563-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Accepted: 04/30/2025] [Indexed: 05/22/2025]
Abstract
BACKGROUND Gastric cancer (GC) is a significant global health issue, with oxidative stress playing a pivotal role in its pathogenesis. Paraoxonase 1 (PON1), an enzyme with antioxidant properties, may modulate oxidative stress and cancer susceptibility. This study examined the association between two PON1 polymorphisms, rs662 (Q192R) and rs854560 (L55M), and their effects on GC risk and oxidative stress markers. METHODS The study included 250 histopathologically confirmed GC patients and 210 healthy controls. PON1 polymorphisms were genotyped, and biochemical markers-including PON1 and arylesterase (ARE) activities, total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI)-were quantified. RESULTS The genotype frequencies of rs854560 and rs662 differed significantly between GC patients and controls. The rs854560 polymorphism was linked to GC risk in co-dominant and dominant inheritance models, while rs662 was associated in co-dominant, dominant, and recessive models. PON1 and ARE activities were significantly reduced in GC patients compared to controls (p = 0.001 and p < 0.001, respectively). TAC was higher in controls (p = 0.006), whereas TOS and OSI showed non-significant trends toward elevation in the GC group (p = 0.093 and p = 0.181, respectively). Genotype stratification revealed significant variations in PON1, ARE, TAC, TOS, and OSI levels across rs854560 and rs662 variants. CONCLUSION Our findings indicate that genetic polymorphisms in PON1, specifically rs662 and rs854560, influence susceptibility to gastric cancer by altering oxidative stress markers. These findings provide insights into how PON1 genetic variations affect oxidative stress and contribute to cancer risk.
Collapse
Affiliation(s)
- Elaheh Najafi
- Department of Clinical Biochemistry, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Farhad Pourfarzi
- Digestive Disease Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Mohammad Mazani
- Department of Clinical Biochemistry, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Abbas Yazdanbod
- Digestive Disease Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Kosar Rezagholizadeh
- Students Research Committee, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Aliakbar Fazaeli
- Department of Clinical Biochemistry, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.
| |
Collapse
|
2
|
Meevassana J, Vongsuly CW, Nakbua T, Kamolratanakul S, Thitiwanichpiwong P, Bin-Alee F, Keelawat S, Kitkumthorn N. Selected Alu methylation levels in the gastric carcinogenesis cascade. PeerJ 2025; 13:e19485. [PMID: 40416611 PMCID: PMC12101442 DOI: 10.7717/peerj.19485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Accepted: 04/27/2025] [Indexed: 05/27/2025] Open
Abstract
Background Genome-wide hypomethylation, a common epigenetic change that occurs during cancer development, primarily affects repetitive elements, such as Alu repeats. Consequently, Alu repeats can be used as a surrogate marker of genomic hypomethylation. Methods In this study, we aimed to investigate the correlation between Alu methylation levels and the multistage course of gastric carcinogenesis. Results We found that the Alu methylation levels in gastric cancer tissue decreased compared with those in normal gastric tissue, with the change in methylation levels and pattern being most significant between chronic gastritis and intestinal metaplasia. Moreover, Alu methylation levels were not associated with Helicobacter pylori or Epstein-Barr virus infection. Conclusions Finally, our sensitivity and specificity analyses suggested that Alu methylation level can be used to distinguish gastric cancer tissue from normal tissue. Thus, Alu methylation level shows promise as biomarker for gastric cancer diagnosis.
Collapse
Affiliation(s)
- Jiraroch Meevassana
- Center of Excellence in Burn and Wound Care, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Chawisa Wanda Vongsuly
- Center of Excellence in Burn and Wound Care, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Tanchanok Nakbua
- Center of Excellence in Burn and Wound Care, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Supitcha Kamolratanakul
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | | | - Fardeela Bin-Alee
- Faculty of Medicine, Princess of Naradhiwas University, Narathiwat, Thailand
| | - Somboon Keelawat
- Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Nakarin Kitkumthorn
- Department of Oral Biology, Faculty of Dentistry, Mahidol University, Bangkok, Thailand
| |
Collapse
|
3
|
Dang Q, Zhang L, Ma H, Sun X, Ren A, Chen J, Huang X, Zhang B, Sun W. Lighthouses illuminating tumor metastasis: The application of fluorescent probes in the localization and imaging metastatic lymph nodes across various tumors. Biomaterials 2025; 316:123020. [PMID: 39693784 DOI: 10.1016/j.biomaterials.2024.123020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 11/24/2024] [Accepted: 12/13/2024] [Indexed: 12/20/2024]
Abstract
The significance of metastatic lymph nodes in tumor diagnosis and prognosis is self-evident. With the deepening of research on the lymphatic system and the advancement of imaging technology, an increasing number of near-infrared fluorescent probes targeting tumor metastatic lymph nodes have been developed. These probes can identify tumors while further detecting lymph nodes (LNs), showcasing great potential in image-guided surgery. In this review, we comprehensively outline the design strategies and applications of near-infrared fluorescent probes for cancers with a high propensity for lymph node metastasis during disease progression. Particular emphasis is placed on two targeting mechanisms: tumor-directed probes capable of identifying metastatic lymph nodes and lymph node-specific probes utilizing passive targeting of metastatic lymph nodes or active targeting of lymph nodes directly. Additionally, we discuss current issues and future prospects in this field, which will facilitate the development of new fluorescent probes and their further clinical translation.
Collapse
Affiliation(s)
- Qi Dang
- College of Medical Laboratory, Dalian Medical University, Dalian, 116044, China
| | - Linhao Zhang
- State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials Oriented Chemical Engineering, Dalian University of Technology, Dalian, 116024, China
| | - Huipeng Ma
- College of Medical Laboratory, Dalian Medical University, Dalian, 116044, China
| | - Xiaoshan Sun
- College of Medical Laboratory, Dalian Medical University, Dalian, 116044, China
| | - Anguo Ren
- College of Medical Laboratory, Dalian Medical University, Dalian, 116044, China
| | - Jiuyang Chen
- College of Medical Laboratory, Dalian Medical University, Dalian, 116044, China
| | - Xiaohua Huang
- College of Medical Laboratory, Dalian Medical University, Dalian, 116044, China
| | - Boyu Zhang
- College of Medical Laboratory, Dalian Medical University, Dalian, 116044, China.
| | - Wen Sun
- State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials Oriented Chemical Engineering, Dalian University of Technology, Dalian, 116024, China.
| |
Collapse
|
4
|
Huang Y, Wang D, Liu Y, Xu X, Chen L, Ma Z, Liu Z. Current research status and hotspots of precancerous lesions of gastric cancer: a bibliometric analysis. Front Oncol 2025; 15:1571617. [PMID: 40365340 PMCID: PMC12069070 DOI: 10.3389/fonc.2025.1571617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Accepted: 03/31/2025] [Indexed: 05/15/2025] Open
Abstract
Background Gastric cancer is the fifth most common cancer worldwide, and its lack of specific symptoms presents a significant challenge for early diagnosis. Therefore, the identification and detection of precancerous lesions of gastric cancer (PLGC) are essential for its prevention. We performed a comprehensive bibliometric analysis to explore the research trends and emerging topics in this field, aiming to deepen our understanding of PLGC. Objective This study utilizes a bibliometric approach with network analysis to explore the progress and trends in PLGC research. The findings aim to provide a foundation and guidance for further in-depth investigations into PLGC. Methods This study used VOSviewer and CiteSpace software to collect relevant literature on PLGC from the Web of Science Core Collection, covering the period from 2005 to 2024. Data visualization analysis was performed on the number of publications, countries, institutions, journals, authors, keywords, and citation counts of these articles. Results A total of 1,141 relevant articles were included in the analysis. The results showed a year-on-year increase in the number of publications from 2005 to 2024. The country, institution, author, and journal with the highest publication output in this field were China, Peking University, Wei-Cheng You, and World Journal of Gastroenterology, respectively. The most frequently occurring keywords in the PLGC field were "Helicobacter pylori," "intestinal metaplasia," "risk," "infection," and "atrophic gastritis." Additionally, "chronic atrophic gastritis" and "inflammation" have emerged as hot topics for future research. Conclusion This bibliometric analysis highlights the hot topics and emerging trends in PLGC research, aiming to provide valuable guidance for future studies. Our findings indicate that mechanistic studies and clinical diagnosis will be key areas of focus in upcoming research.
Collapse
Affiliation(s)
- Yan Huang
- First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
| | - Dexin Wang
- Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (TCM), Institute of Liver Diseases, Cell Biology Laboratory, Shanghai University of TCM, Key Laboratory of Liver and Kidney Disease of the Ministry of Education, Clinical Key Laboratory of TCM of Shanghai, Shanghai, China
| | - Yuzhuo Liu
- Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, China
| | - Xiaonan Xu
- First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
| | - Li Chen
- Neonatology Department, Qiqihar Traditional Chinese Medicine Hospital, Qiqihar, China
| | - Zhuolin Ma
- Heilongjiang Eye Hospital, Harbin, China
| | - Zhaoxia Liu
- First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
| |
Collapse
|
5
|
Chen D, Wang W, Chen X, Liang N, Li J, Ding W, Zhang H, Yang Z, Zhao H, Liu Z. Plant-derived extracts or compounds for Helicobacter-associated gastritis: a systematic review of their anti-Helicobacter activity and anti-inflammatory effect in animal experiments. Chin Med 2025; 20:53. [PMID: 40264171 PMCID: PMC12013188 DOI: 10.1186/s13020-025-01093-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 03/10/2025] [Indexed: 04/24/2025] Open
Abstract
BACKGROUND Helicobacter infection, which is the leading cause of gastritis and stomach cancer, has become common worldwide. Almost all Helicobacter-infected patients have chronic active gastritis, also known as Helicobacter-associated gastritis (HAG). However, the eradication rate of Helicobacter is decreasing due to the poor efficacy of current medications, which causes infection to recur, inflammation to persist, and stomach cancer to develop. Natural components have robust antibacterial activity and anti-inflammatory capacity, as confirmed by many studies of alternative natural medicines. PURPOSE This article aimed to conduct a comprehensive search and meta-analysis to evaluate the efficacy of anti-Helicobacter and anti-inflammatory activities of plant-derived extracts or compounds that can treat HAG in animal experiments. We intended to provide detailed preclinical-research foundation including plant and compound information, as well as the mechanisms by which these plant-derived substances inhibit the progression of Helicobacter infection, gastritis and neoplasms for future study. METHODS The systematic review is aligned with the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, and the protocol was registered in PROSPERO (CRD42024527889). An extensive search was performed across multiple databases, including PubMed, Scopus, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), the Chinese Scientific Journal database (VIP), the Wanfang database, and the China biomedical literature service system (SinoMed), up until November 2023. Meta-analysis on Review Manager software (RevMan 5.4) estimating anti-Helicobacter and anti-inflammatory activity was performed. We used the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) risk of bias tool to evaluate the risk of bias of each study included. RESULTS Our study encompassed 61 researches, comprised 36 extracts and 37 compounds improving HAG by inhibiting Helicobacter infection, the inflammatory response, oxidative stress, and regulating apoptosis and proliferation. Sixteen families especially Asteraceae, Fabaceae and Rosaceae and nine classes including Terpenoids, Alkaloids, Phenols, and Flavonoids may be promising directions for valuable new drugs. The Meta-analyse demonstrated the plant-base substance treatments possess significant anti-Helicobacter and anti-inflammation activity comparing to control groups. The included plants and compounds confirmed that signaling pathways NF-κB, JAK2/STAT3, MAPK, TLR4/MyD88, PI3K/AKT, NLRP3/Caspase-1 and NRF2/HO-1 play a key role in the progression of HAG. CONCLUSION Plant-derived extracts or compounds actively improve HAG by modulating relevant mechanisms and signaling pathways, particularly through the anti-Helicobacter and inflammatory regulation ways. Further researches to apply these treatments in humans are needed, which will provide direction for the future development of therapeutic drugs to increase eradication rate and alleviate gastritis.
Collapse
Affiliation(s)
- Danni Chen
- College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, China
| | - Wenlai Wang
- Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, No. 16 Nanxiaojie, Dongzhimen Nei, Dongcheng District, Beijing, 100700, China
| | - Xiangyun Chen
- College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, China
| | - Ning Liang
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Jiawang Li
- College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, China
| | - Wei Ding
- College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, China
| | - Hongrui Zhang
- Dongzhimen Hospital, Beijing University of Chinese Medicine, No. 5 Haiyuncang, Dongcheng District, Beijing, 100700, China
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Zhen Yang
- College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, China.
| | - Hongxia Zhao
- Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, No. 16 Nanxiaojie, Dongzhimen Nei, Dongcheng District, Beijing, 100700, China.
| | - Zhenhong Liu
- Dongzhimen Hospital, Beijing University of Chinese Medicine, No. 5 Haiyuncang, Dongcheng District, Beijing, 100700, China.
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, 100700, China.
| |
Collapse
|
6
|
Poornima E, Chandra E, Rajendran P, Pankajavalli PB. Stomach cancer identification based on exhaled breath analysis: a review. J Breath Res 2025; 19:024002. [PMID: 40190017 DOI: 10.1088/1752-7163/adc979] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Accepted: 04/04/2025] [Indexed: 04/16/2025]
Abstract
Early prediction of cancer is crucial for effective treatment decisions. Stomach cancer is one of the worst malignancies in the world because it does not reveal the growth in symptoms. In recent years, non-invasive diagnostic methods, particularly exhaled breath analysis, have attracted interest in detecting stomach cancer. This review discusses invasive and non-invasive diagnostic methods for stomach cancer, with a special emphasis on breath analysis and electronic nose (e-nose) technology. Various analytical methods have been used to analyze volatile organic compounds (VOCs) associated with stomach cancer. Gas chromatography-mass Spectrometry is one of the most widely used techniques. These techniques enable the detection and analysis of VOCs, offering a promising route for early stomach cancer diagnosis. The e-nose system has been introduced as a cost-effective and portable alternative for VOC detection in stomach cancer to overcome the challenges associated with conventional methods. This review discusses the advantages and disadvantages of the e-nose system. This review recommends that e-nose sensors, combined with advanced pattern recognition techniques, be utilized to enable rapid and reliable diagnosis of stomach cancer.
Collapse
Affiliation(s)
- E Poornima
- Department of Computer Science, Bharathiar University, Coimbatore, Tamil Nadu, India
| | - E Chandra
- Department of Computer Science, Bharathiar University, Coimbatore, Tamil Nadu, India
| | - Porkodi Rajendran
- Department of Computer Science, Bharathiar University, Coimbatore, Tamil Nadu, India
| | - P B Pankajavalli
- Department of Computer Science, Bharathiar University, Coimbatore, Tamil Nadu, India
| |
Collapse
|
7
|
Kong X, Li C, Li Y, Song X, Huang L. Ultrasensitive determination of exosomes by tyramine-assisted colorimetric sensors for tumor diagnosis. Analyst 2025; 150:1670-1678. [PMID: 40111754 DOI: 10.1039/d5an00013k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/22/2025]
Abstract
Exosomes, which are recognized as a kind of valuable liquid biopsy biomarker, exhibit significant application potential in cancer diagnosis. Therefore, it is crucial to establish a reliable detection method for their clinical application. In this study, we have presented an ultrasensitive aptasensor for the visual detection of exosomes by employing tyramine-assisted dual-signal amplification technology. First, we utilized magnetic beads modified with the nucleolin aptamer (MNPs-Aptnucleolin) to capture exosomes. This modification not only enhanced specificity, but also reduced interference of complex sample components. The captured exosomes as a rich source of proteins can bind with multiple biotinyl-tyramide (Bio-TR) molecules through a catalytic reaction involving horseradish peroxidase (HRP) and H2O2. Second, streptavidin-HRP complex-modified gold nanoparticles (GNPs-Str-HRP) as a signal amplification probe was introduced to further enhance the detection signal by binding to Bio-TR. Lastly, the addition of 3,3',5,5'-tetramethylbenzidine (TMB) solution induced a visible color change, enabling quantification of the exosome concentration. This dual-signal amplification strategy resulted in a low limit of detection (LOD) of 63 particles per μL, and it also demonstrated accurate visual diagnosis capabilities for clinical samples. The successful implementation of this approach suggests its potential as a promising tool for point-of-care testing (POCT) in cancer diagnostics.
Collapse
Affiliation(s)
- Xiaoming Kong
- Affiliated Psychological Hospital of Anhui Medical University, Anhui Mental Health Center, Hefei Fourth People's Hospital, 316 Huangshan Road, Hefei, 230022, China
| | - Chao Li
- School of Life Sciences, Anhui Medical University, Hefei, Anhui 230032, China.
| | - Yang Li
- School of Life Sciences, Anhui Medical University, Hefei, Anhui 230032, China.
| | - Xueqian Song
- School of Life Sciences, Anhui Medical University, Hefei, Anhui 230032, China.
| | - Lin Huang
- School of Life Sciences, Anhui Medical University, Hefei, Anhui 230032, China.
| |
Collapse
|
8
|
Zhang J, Wang G, Xie X, Pan W, Dong Q, Zhang N, Dong J, Zhou L, Zhou C, Li J, Segall G, Zhang Y. Treatment patterns and outcomes in advanced or metastatic gastric/gastroesophageal junction adenocarcinoma in China. Future Oncol 2025; 21:1179-1188. [PMID: 40091795 PMCID: PMC11988209 DOI: 10.1080/14796694.2025.2476930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Accepted: 03/05/2025] [Indexed: 03/19/2025] Open
Abstract
AIMS Describe the characteristics, treatment patterns and outcomes of Chinese patients with unresectable advanced/metastatic (UAM) gastric/gastroesophageal junction adenocarcinoma (GA/GEJA). METHODS This multicenter, retrospective, observational study included adults diagnosed with UAM GA/GEJA in China from 2017-2020. RESULTS Among 2,745 patients, 1,902, 729, and 284 received first-, second- and third-line (1 L, 2 L and 3 L) therapy-respectively. Most patients received chemotherapy alone in 1 L (84.1%) and 2 L (63.6%), and targeted-therapy-based treatment in 3 L (49.2%). Median real-world progression-free survival (rwPFS) was 6.5, 4.2, and 3.2 months in 1 L, 2 L, and 3 L, respectively. CONCLUSIONS Chinese patients with UAM GA/GEJA mainly received chemotherapy alone in 1 L/2 L and targeted therapy in 3 L. Median rwPFS was short in all lines, highlighting the need for more effective treatments.
Collapse
Affiliation(s)
- Jingdong Zhang
- Medical Oncology Department of Gastrointestinal Cancer, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, China
| | - Guangyu Wang
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China
| | - Xianhe Xie
- Department of Medical Oncology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Wensheng Pan
- Cancer Center, Department of Gastroenterology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Qian Dong
- Medical Oncology Department of Gastrointestinal Cancer, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, China
| | - Nianhai Zhang
- Department of Medical Oncology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Jie Dong
- Cancer Center, Department of Gastroenterology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Li Zhou
- Lilly China Drug Development and Medical Affairs Center, Eli Lilly and Company, Shanghai, China
| | - Chan Zhou
- Lilly China Drug Development and Medical Affairs Center, Eli Lilly and Company, Shanghai, China
| | - Jinnan Li
- Lilly China Drug Development and Medical Affairs Center, Eli Lilly and Company, Shanghai, China
| | - Grace Segall
- Value, Evidence and Outcomes, Eli Lilly and Company, Indianapolis, IN, USA
| | - Yanqiao Zhang
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China
| |
Collapse
|
9
|
Zhou L, Su B, Shan Z, Gao Z, Guo X, Wang W, Wang X, Sun W, Yuan S, Sun S, Zhang J, Xu G, Lin X. Metabolic Reprogramming of Gastric Cancer Revealed by a Liquid Chromatography-Mass Spectrometry-Based Metabolomics Study. Metabolites 2025; 15:222. [PMID: 40278351 PMCID: PMC12029534 DOI: 10.3390/metabo15040222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2025] [Revised: 03/08/2025] [Accepted: 03/17/2025] [Indexed: 04/26/2025] Open
Abstract
BACKGROUND/OBJECTIVES Gastric cancer (GC) is a prevalent malignant tumor worldwide, with its pathological mechanisms largely unknown. Understanding the metabolic reprogramming associated with GC is crucial for the prevention and treatment of this disease. This study aims to identify significant alterations in metabolites and pathways related to the development of GC. METHODS A liquid chromatography-mass spectrometry-based non-targeted metabolomics data acquisition was performed on paired tissues from 80 GC patients. Differences in metabolic profiles between tumor and adjacent normal tissues were first investigated through univariate and multivariate statistical analyses. Additionally, differential correlation network analysis and a newly proposed network analysis method (NAM) were employed to explore significant metabolite pathways and subnetworks related to tumorigenesis and various TNM stages of GC. RESULTS Over half of the annotated metabolites exhibited significant alterations. Phosphatidylcholine (PC)_30_0 and fatty acid C20_3 demonstrated strong diagnostic performance for GC, with AUCs of 0.911 and 0.934 in the discovery and validation sets, respectively. Differential correlation network analysis revealed significant fatty acid-related metabolic reprogramming in GC with elevated levels of medium-chain acylcarnitines and increased activity of medium-chain acyl-CoA dehydrogenase, firstly observed in clinical GC tissues. Of note, using NAM, two correlation subnetworks were identified as having significant alterations across different TNM stages, centered with choline and carnitine C4_0-OH, respectively. CONCLUSIONS The identified significant alterations in fatty acid metabolism and TNM-related metabolic subnetworks in GC tissues will facilitate future investigations into the metabolic reprogramming associated with gastric cancer.
Collapse
Affiliation(s)
- Lina Zhou
- School of Computer Science and Technology, Dalian University of Technology, Dalian 116024, China; (L.Z.); (B.S.); (Z.G.); (W.W.); (W.S.)
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China; (X.G.); (X.W.); (G.X.)
- Instrumental Analysis Center, Dalian University of Technology, Dalian 116024, China
| | - Benzhe Su
- School of Computer Science and Technology, Dalian University of Technology, Dalian 116024, China; (L.Z.); (B.S.); (Z.G.); (W.W.); (W.S.)
| | - Zexing Shan
- Department of Gastric Surgery, Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital & Institute), Shenyang 110042, China;
| | - Zhenbo Gao
- School of Computer Science and Technology, Dalian University of Technology, Dalian 116024, China; (L.Z.); (B.S.); (Z.G.); (W.W.); (W.S.)
| | - Xingyu Guo
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China; (X.G.); (X.W.); (G.X.)
| | - Weiwei Wang
- School of Computer Science and Technology, Dalian University of Technology, Dalian 116024, China; (L.Z.); (B.S.); (Z.G.); (W.W.); (W.S.)
| | - Xiaolin Wang
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China; (X.G.); (X.W.); (G.X.)
| | - Wenli Sun
- School of Computer Science and Technology, Dalian University of Technology, Dalian 116024, China; (L.Z.); (B.S.); (Z.G.); (W.W.); (W.S.)
| | - Shuai Yuan
- Central Laboratory, Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital & Institute), Shenyang110042, China; (S.Y.); (S.S.)
| | - Shulan Sun
- Central Laboratory, Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital & Institute), Shenyang110042, China; (S.Y.); (S.S.)
| | - Jianjun Zhang
- Department of Gastric Surgery, Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital & Institute), Shenyang 110042, China;
| | - Guowang Xu
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China; (X.G.); (X.W.); (G.X.)
- Liaoning Province Key Laboratory of Metabolomics, Dalian 116023, China
| | - Xiaohui Lin
- School of Computer Science and Technology, Dalian University of Technology, Dalian 116024, China; (L.Z.); (B.S.); (Z.G.); (W.W.); (W.S.)
| |
Collapse
|
10
|
黄 晴, 张 文, 张 小, 王 炼, 宋 雪, 耿 志, 左 芦, 王 月, 李 静, 胡 建. [High MYO1B expression promotes proliferation, migration and invasion of gastric cancer cells and is associated with poor patient prognosis]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2025; 45:622-631. [PMID: 40159977 PMCID: PMC11955900 DOI: 10.12122/j.issn.1673-4254.2025.03.20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Indexed: 04/02/2025]
Abstract
OBJECTIVES To analyze MYO1B expression in gastric cancer, its association with long-term prognosis and its role in regulating biological behaviors of gastric cancer cells. METHODS We analyzed MYO1B expression in gastric cancer and its correlation with tumor grade, tumor stage, and patient survival using the Cancer Public Database. We also examined MYO1B expression with immunohistochemistry in gastric cancer and paired adjacent tissues from 105 patients receiving radical surgery and analyzed its correlation with cancer progression and postoperative 5-year survival of the patients. GO and KEGG enrichment analyses were used to explore the biological functions of MYO1B and the key pathways. In cultured gastric cancer cells, we examined the changes in cell proliferation, migration and invasion following MYO1B overexpression and knockdown. RESULTS Data from the Cancer Public Database showed that MYO1B expression was significantly higher in gastric cancer tissues than in normal tissues with strong correlations with tumor grade, stage and patient prognosis (P<0.05). In the clinical tissue samples, MYO1B was significantly overexpressed in gastric cancer tissues in positive correlation with Ki67 expression (r=0.689, P<0.05) and the parameters indicative of gastric cancer progression (CEA ≥5 μg/L, CA19-9 ≥37 kU/L, G3-4, T3-4, and N2-3) (P<0.05). Kaplan-Meier analysis and multivariate Cox regression analysis suggested that high MYO1B expression was associated with decreased postoperative 5-year survival and was an independent risk factor (HR: 3.522, 95%CI: 1.783-6.985, P<0.05). MYO1B expression level was a strong predictor of postoperative survival (cut-off value: 3.11, AUC: 0.753, P<0.05). GO and KEGG analyses suggested that MYO1B may regulate cell migration and the mTOR signaling pathway. In cultured gastric cancer cells, MYO1B overexpression significantly enhanced cell proliferation, migration, and invasion and promoted the phosphorylation of Akt and mTOR. CONCLUSIONS High MYO1B expression promotes proliferation, migration and invasion of gastric cancer cells and is correlated with poor patient prognosis.
Collapse
|
11
|
Yuan Z, Wang JH, Cui H, Wang SY, Wei B, Cui JX. Mapping the landscape of gastric cancer immunotherapy: Bibliometric insights into advances and hotspots. World J Gastrointest Oncol 2025; 17:100997. [PMID: 40092931 PMCID: PMC11866247 DOI: 10.4251/wjgo.v17.i3.100997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Revised: 12/11/2024] [Accepted: 12/31/2024] [Indexed: 02/14/2025] Open
Abstract
BACKGROUND Immunotherapy has surfaced as a promising therapeutic modality for gastric cancer (GC). A comprehensive review of advancements, current status, and research trends in GC immunotherapy is essential to inform future investigative efforts. AIM To delineate the trends, advancements, and focal points in immunotherapy for GC. METHODS We performed a bibliometric analysis of 2906 articles in English concerning GC immunotherapy published from 2000 to December 20, 2023, indexed in the Web of Science Core Collection. Data analysis and visualization were facilitated by CiteSpace (6.1.6R), VOSviewer v.1.6.17, and GraphPad Prism v8.0.2. RESULTS There has been an increase in the annual publication rate of GC immunotherapy research. China leads in publication volume, while the United States demonstrates the highest citation impact. Fudan University is notable for its citation frequency and publication output. Co-citation analysis and keyword frequency revealed and highlighted a focus on GC prognosis, the tumor microenvironment (TME), and integrative immunotherapy with targeted therapy. Emerging research areas include gastroesophageal junction cancer, adoptive immunotherapy, and the role of Treg cell in immunotherapy. CONCLUSION GC immunotherapy research is an expanding field attracting considerable scientific interest. With the clinical adoption of immunotherapy in GC, the primary goals are to enhance treatment efficacy and patient outcomes. Unlike hematological malignancies, GC's solid TME presents distinct immunological challenges that may attenuate the cytotoxic effects of immune cells on cancer cells. For instance, although CAR-T therapy is effective in hematological malignancies, it has underperformed in GC settings. Current research is centered on overcoming immunosuppression within the TME, with a focus on combinations of targeted therapy, adoptive immunotherapy, Treg cell dynamics, and precise prognosis prediction in immunotherapy. Additionally, immunotherapy's role in treating gastroesophageal junction cancer has become a novel research focus.
Collapse
Affiliation(s)
- Zhen Yuan
- School of Medicine, Nankai University, Tianjin 300071, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Jing-Hang Wang
- School of Medicine, Nankai University, Tianjin 300071, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Hao Cui
- School of Medicine, Nankai University, Tianjin 300071, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Shu-Yuan Wang
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Bo Wei
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Jian-Xin Cui
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| |
Collapse
|
12
|
Sun HT. Helicobacter pylori-related serum indicators: Cutting-edge advances to enhance the efficacy of gastric cancer screening. World J Gastrointest Oncol 2025; 17:100739. [PMID: 40092953 PMCID: PMC11866254 DOI: 10.4251/wjgo.v17.i3.100739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 12/08/2024] [Accepted: 01/03/2025] [Indexed: 02/14/2025] Open
Abstract
Helicobacter pylori (H. pylori) infection induces pathological changes via chronic inflammation and virulence factors, thereby increasing the risk of gastric cancer development. Compared with invasive examination methods, H. pylori-related serum indicators are cost-effective and valuable for the early detection of gastric cancer (GC); however, large-scale clinical validation and sufficient understanding of the specific molecular mechanisms involved are lacking. Therefore, a comprehensive review and analysis of recent advances in this field is necessary. In this review, we systematically analyze the relationship between H. pylori and GC and discuss the application of new molecular biomarkers in GC screening. We also summarize the screening potential and application of anti-H. pylori immunoglobulin G and virulence factor-related serum antibodies for identifying GC risk. These indicators provide early warning of infection and enhance screening accuracy. Additionally, we discuss the potential combination of multiple screening indicators for the comprehensive analysis and development of emerging testing methods to improve the accuracy and efficiency of GC screening. Although this review may lack sufficient evidence due to limitations in existing studies, including small sample sizes, regional variations, and inconsistent testing methods, it contributes to advancing personalized precision medicine in high-risk populations and developing GC screening strategies.
Collapse
Affiliation(s)
- Hao-Tian Sun
- Cancer Institute, University College London, London WC1E 6BT, United Kingdom
| |
Collapse
|
13
|
Moratorio I, Canavesi A, Olano C, Mönkemüller K. Prevalence and endoscopic-histological correlation of premalignant gastric lesions at a university hospital in Uruguay. Endosc Int Open 2025; 13:a25420880. [PMID: 40109312 PMCID: PMC11922308 DOI: 10.1055/a-2542-0880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Accepted: 02/14/2025] [Indexed: 03/22/2025] Open
Abstract
Background and study aims Although chronic atrophic gastritis (CAG), intestinal metaplasia (IM), and dysplasia constitute gastric pre-neoplastic conditions of gastric cancer (GC), data on endoscopic correlation and the prevalence in many South American countries are scarce. The aims of this study were to establish prevalence and perform endoscopic-histological correlation of gastric pre-neoplastic conditions using high-definition white light endoscopy (WLE) and to determine interobserver agreement for endoscopic findings for CAG and IM. Patients and methods A prospective, observational, descriptive, cross-sectional study was carried out at a Uruguayan hospital during a 6-month period. Risk was stratified according to Operative Link for Gastritis Assessment and Operative Link for Gastric Intestinal Metaplasia stage for CAG and IM, respectively. An independent and blinded second observer was included to determine interobserver endoscopic and histologic agreement. Results A total of 102 patients (mean age 57 years ± 1.6 years, 68.6% woman) were included. Prevalence of histological CAG and IM were 38.2% and IM 31.4%, respectively. Endoscopic-histological correlation for CAG had kappa index 0.063, sensitivity 46%, and specificity 60%. For endoscopic IM, the kappa index was 0.216, sensitivity 22%, and specificity 96%. Interobserver variability was good for gastric fold flattening and very good in the presence of whitish-greyish plaques for CAG and IM, respectively. Conclusions The endoscopic-histological correlation of both CAG and IM was low, raising the need for biopsy for diagnosis in all cases, regardless of HD-WLE findings. Although prevalence of gastric pre-neoplastic conditions in this group of Uruguayan patients was comparable to those described in countries with a high incidence of GC, a low proportion of high-risk stages (III and IV) was identified.
Collapse
Affiliation(s)
- Ignacio Moratorio
- Unidad Académica Gastroenterología, Hospital de Clinicas Doctor Manuel Quintela, Montevideo, Uruguay
| | - Adrian Canavesi
- Unidad Académica Gastroenterología, Hospital de Clinicas Doctor Manuel Quintela, Montevideo, Uruguay
| | - Carolina Olano
- Unidad Académica Gastroenterología, Hospital de Clinicas Doctor Manuel Quintela, Montevideo, Uruguay
| | - Klaus Mönkemüller
- Unidad Académica Gastroenterología, Hospital de Clinicas Doctor Manuel Quintela, Montevideo, Uruguay
| |
Collapse
|
14
|
Jiang W, Yin F, Bian X, Wang Z, Zhang C. The mechanism study of LncRNA AC012181.2 targeting HERPUD1 protein in regulating stromal stem cells participating in metabolic reprogramming for gastric cancer metastasis. Int Immunopharmacol 2025; 148:113978. [PMID: 39879832 DOI: 10.1016/j.intimp.2024.113978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Revised: 12/24/2024] [Accepted: 12/28/2024] [Indexed: 01/31/2025]
Abstract
OBJECTIVE To investigate the role of long non-coding RNAs (lncRNAs) in the metabolic reprogramming of gastric cancer through their regulation of mesenchymal stem cells (MSCs) and HERPUD1 protein targets, aiming to elucidate mechanisms that could lead to novel therapeutic strategies. METHOD The RNA-seq was performed on BGC and hMSC-BGC cells to perform LncRNA screening. And we employed cell culture techniques using hMSC-BM and BGC823 cells, treated with various genetic interventions including siRNA and overexpression vectors. Techniques such as cell viability assays, quantitative PCR (qPCR), Western blotting, RNA pull-down and RNA-FISH were utilized to validate the interaction between lncRNA AC012181.2 and HERPUD1 protein. Flow cytometry were utilized to analyze the impacts of lncRNA AC012181.2 on gene and protein expression related to cancer metabolism. Additionally, a tumorigenic model in nude mice was used to observe the in vivo effects. RESULT Modulation of AC012181.2 in MSCs significantly affected the proliferation, migration, and invasion capabilities of BGC823 gastric cancer cells. Knockdown of AC012181.2 resulted in reduced tumor growth in mouse models, along with changes in key gene and protein expression levels associated with cancer metabolism. Overexpression of AC012181.2 showed the opposite effect, enhancing tumor growth and altering cellular behaviors and molecular expressions in favor of cancer progression. CONCLUSION The lncRNA AC012181.2 is crucial for gastric cancer metabolic reprogramming by regulating HERPUD1 Protein. Targeting it offers a promising avenue to impact the tumor microenvironment and develop novel gastric cancer therapies.
Collapse
Affiliation(s)
- Weidong Jiang
- Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, No.4026, Yatai Street, Nanguan District, Changchun 130000, China
| | - Fangying Yin
- Department of Pediatrics, The Third Norman Bethune Hospital of Jilin University, Xiantai Street, NO.126, Changchun 130033, China
| | - Xuming Bian
- Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, No.4026, Yatai Street, Nanguan District, Changchun 130000, China
| | - Zhenxiao Wang
- Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, No.4026, Yatai Street, Nanguan District, Changchun 130000, China
| | - Chaohe Zhang
- Department of Tumor Hematology, The Second Hospital of Jilin University, No.4026, Yatai Street, Nanguan District, Changchun 130000, China.
| |
Collapse
|
15
|
Wu HM, Ying XX, Lv LL, Hu JW. Diagnostic implications of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic immune-inflammatory index for gastric carcinoma. World J Gastrointest Surg 2025; 17:100130. [PMID: 39872777 PMCID: PMC11757178 DOI: 10.4240/wjgs.v17.i1.100130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 09/19/2024] [Accepted: 09/27/2024] [Indexed: 12/27/2024] Open
Abstract
BACKGROUND The diagnosis of gastric carcinoma (GC) is essential for improving clinical outcomes. However, the biomarkers currently used for GC screening are not ideal. AIM To explore the diagnostic implications of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammatory index (SII) for GC. METHODS The baseline data of 133 patients with GC and 134 patients with precancerous gastric conditions admitted between January 2022 and December 2023 were retrospectively analyzed. The information on peripheral blood platelet, neutrophil, and lymphocyte counts in each patient was collected, and the NLR, PLR, and SII levels of both groups were calculated. Additionally, multivariate logistic regression analysis was conducted, and the diagnostic implications of NLR, PLR, and SII in differentiating patients with precancerous gastric conditions, compared with those with GC, were analyzed through receiver operating characteristic (ROC) curves. RESULTS The data indicated that NLR, PLR, and SII had abnormally increased levels in the patients with GC. Gender and body mass index were risk factors for the occurrence of GC. ROC data revealed that the areas under the curve of three patients with precancerous gastric conditions, who were differentiated from those with GC, were 0.824, 0.787, and 0.842, respectively. CONCLUSION NLR, PLR, and SII are all abnormally expressed in GC and have diagnostic implications, especially when used as joint indicators, in distinguishing patients with precancerous gastric conditions from those with GC.
Collapse
Affiliation(s)
- Huang-Min Wu
- Department of Gastroenterology, Dongyang People's Hospital, Dongyang 322100, Zhejiang Province, China
| | - Xiao-Xuan Ying
- Department of Gastroenterology, Dongyang People's Hospital, Dongyang 322100, Zhejiang Province, China
| | - Li-Li Lv
- Department of Gastroenterology, Dongyang People's Hospital, Dongyang 322100, Zhejiang Province, China
| | - Jian-Wen Hu
- Department of Gastroenterology, Dongyang People's Hospital, Dongyang 322100, Zhejiang Province, China
| |
Collapse
|
16
|
Werawatganone P, Werawatganon D, Noonak N, Chayanupatkul M, Chatsuwan T, Klaikeaw N, Muangsiri W, Siriviriyakul P. Unveiling the Potency of Gardenia Extract Against H. pylori: Insights from In Vitro and In Vivo Studies. Biomedicines 2025; 13:92. [PMID: 39857676 PMCID: PMC11760463 DOI: 10.3390/biomedicines13010092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2024] [Revised: 12/24/2024] [Accepted: 12/31/2024] [Indexed: 01/27/2025] Open
Abstract
BACKGROUND AND AIM Gardenia jasminoides (G. jasminoides) could treat various inflammatory diseases. This study aimed to investigate the effects of G. jasminoides fruit extract on gastric inflammation and protective mechanisms in Helicobacter pylori (H. pylori)-induced gastritis. Experimental procedure: G. jasminoides fruit extract was prepared and analyzed for geniposide content. The inhibitory effect of the extract on H. pylori growth was investigated using the disk diffusion method. The in vitro anti-inflammatory property of the extract was evaluated using the erythrocyte membrane stabilization method. Thirty-five male Sprague-Dawley rats were inoculated with H. pylori (108-1010 colony-forming unit/mL) and divided into five groups. Each group was treated with various doses of the extract (98-395 mg/kg). The serum and stomach tissue of the rats were evaluated using enzyme-linked immunosorbent assay, histopathology, and immunohistochemistry. RESULTS AND CONCLUSIONS The geniposide content in the dried extract was 8.12% ± 0.79% by dry weight. The inhibition zone was observed at the extract ≥ 1.97 mg/disk, and the extract presented anti-inflammatory potential. The H. pylori-inoculated rats had a significant increase in serum interleukin (IL)-17, IL-33, and gastric epidermal growth factor (EGF) levels and a significant decrease in serum prostaglandin E2 level (p < 0.05) in conjunction with the development of gastric inflammation on histopathology. The treatment of the extract could significantly decrease the serum IL-17, IL-33, and gastric EGF levels, significantly increase the serum PGE2 level (p < 0.05), and improve gastric histopathology. Thus, G. jasminoides fruit extract attenuated H. pylori-induced gastritis by inhibiting bacterial growth, reducing inflammation, and enhancing protective mechanisms.
Collapse
Affiliation(s)
- Pornpen Werawatganone
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand; (P.W.); (W.M.)
| | - Duangporn Werawatganon
- Center of Excellence in Alternative and Complementary Medicine for Gastrointestinal and Liver Diseases, Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand (M.C.)
| | - Nattida Noonak
- Center of Excellence in Alternative and Complementary Medicine for Gastrointestinal and Liver Diseases, Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand (M.C.)
| | - Maneerat Chayanupatkul
- Center of Excellence in Alternative and Complementary Medicine for Gastrointestinal and Liver Diseases, Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand (M.C.)
| | - Tanittha Chatsuwan
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Naruemon Klaikeaw
- Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand;
| | - Walaisiri Muangsiri
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand; (P.W.); (W.M.)
| | - Prasong Siriviriyakul
- Center of Excellence in Alternative and Complementary Medicine for Gastrointestinal and Liver Diseases, Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand (M.C.)
| |
Collapse
|
17
|
Gao R, Hu Y, Yuan Q. ADAMTS12 serves as a novel prognostic biomarker and promotes proliferation and invasion in gastric cancer. Discov Oncol 2024; 15:837. [PMID: 39720953 DOI: 10.1007/s12672-024-01724-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Accepted: 12/18/2024] [Indexed: 12/26/2024] Open
Abstract
Gastric cancer (GC) remains a prevalent and aggressive malignancy with a poor prognosis. This study aimed to identify diagnostic and prognostic biomarkers while exploring their potential functions in GC. A total of 598 upregulated and 506 downregulated genes were identified in GC patients. Among these, survival-related differentially expressed genes (DEGs), including ADAMTS12, F5, and VCAN, were highlighted. Pan-cancer analyses revealed their dysregulation across multiple tumor types. A novel prognostic signature, incorporating ADAMTS12 and F5, effectively stratified GC patients into low- and high-risk groups, demonstrating significant differences in overall survival and robust predictive performance. ADAMTS12, strongly associated with advanced clinical stages and poor prognosis, was validated in an independent cohort and exhibited promising diagnostic potential. RT-PCR and western blot analyses confirmed its high expression in GC tissues and cell lines. Functional assays further demonstrated that ADAMTS12 promotes GC cell proliferation and invasion. In summary, this study provides critical insights into the molecular landscape of GC, offering a potential prognostic tool and therapeutic target.
Collapse
Affiliation(s)
- Ruimei Gao
- Department of Gastroenterology, Qingdao Chengyang People's Hospital, Qingdao, China
| | - Yalan Hu
- Department of Anorectal Surgery, Qingdao Eighth People's Hospital, Qingdao, China
| | - Qiuxiang Yuan
- Department of Gastroenterology, Qingdao Chengyang People's Hospital, Qingdao, China.
| |
Collapse
|
18
|
Yuan J, Gu W, Xu T, Zhang Y, Shen L, Yan J, Guan X, Chu H, Yuan R, Ju S. Dysregulated transfer RNA-derived small RNAs as potential gastric cancer biomarkers. Exp Biol Med (Maywood) 2024; 249:10170. [PMID: 39735780 PMCID: PMC11673218 DOI: 10.3389/ebm.2024.10170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Accepted: 11/07/2024] [Indexed: 12/31/2024] Open
Abstract
Gastric cancer (GC) is the kind of carcinoma that has the highest rates of morbidity and death worldwide. In the early stages of GC, there is currently an absence of sensitive and specific biomarkers. The newly-discovered class of non-coding RNAs (ncRNAs) known as transfer RNA-derived small RNAs (tsRNAs) is highly expressed in bodily fluids and neoplastic cells. High-throughput sequencing was initially employed to identify differentially expressed tsRNAs in early GC patients, followed by validation in patient serum, GC tissues, and cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). We identified dysregulated tsRNAs (the up-regulated tsRNAs included tRF-31-PNR8YP9LON4VD, tRF-30-MIF91SS2P4FI, and tRF-30-IK9NJ4S2I7L7, whereas the down-regulated tsRNAs included tRF-38-W6RM7KYUPRENRHD2, tRF-37-LBRY73W0K5KKOV2, tRF-36-JB59V3WD8YQ84VD, tRF-25-MBQ4NKKQBR, and tRF-36-0KFMNKYUHRF867D) in GC, and we verified that the serum of patients, GC cells and tissues both consistently expressed these tsRNAs. Additionally, GC patients' serum had considerably greater expression levels of the three up-regulated tsRNAs than did healthy controls. Receiver operating characteristic (ROC) curve analysis demonstrated that the sensitivity and specificity of the three up-regulated tsRNAs were superior to those of CEA, CA199, and CA724 in the process of diagnosing GC, particularly in its early stages. This suggests that tsRNAs have great diagnostic efficacy and potential as new "liquid biopsy" biomarkers for the diagnosis of GC. Using bioinformatics software, we predicted that dysregulation of tsRNAs may be a potential regulatory mechanism for the development of GC.
Collapse
Affiliation(s)
- Jie Yuan
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong University, Nantong, China
| | - Wenchao Gu
- Department of Special Laboratory Center, Affiliated Hospital of Nantong University, Nantong University, Nantong, China
| | - Tianxin Xu
- Department of General Surgery, Affiliated Hospital of Nantong University, Nantong University, Nantong, China
| | - Yan Zhang
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong University, Nantong, China
| | - Lei Shen
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong University, Nantong, China
| | - Jianliang Yan
- Medical School of Nantong University, Nantong University, Nantong, China
| | - Xi Guan
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong University, Nantong, China
| | - Haidan Chu
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong University, Nantong, China
| | - Ruoyu Yuan
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong University, Nantong, China
| | - Shaoqing Ju
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong University, Nantong, China
| |
Collapse
|
19
|
Lee H, Chung JW, Yun SC, Jung SW, Yoon YJ, Kim JH, Cha B, Kayasseh MA, Kim KO. Validation of Artificial Intelligence Computer-Aided Detection on Gastric Neoplasm in Upper Gastrointestinal Endoscopy. Diagnostics (Basel) 2024; 14:2706. [PMID: 39682614 DOI: 10.3390/diagnostics14232706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Revised: 11/22/2024] [Accepted: 11/25/2024] [Indexed: 12/18/2024] Open
Abstract
BACKGROUND/OBJECTIVES Gastric cancer ranks fifth for incidence and fourth in the leading causes of mortality worldwide. In this study, we aimed to validate previously developed artificial intelligence (AI) computer-aided detection (CADe) algorithm, called ALPHAON® in detecting gastric neoplasm. METHODS We used the retrospective data of 500 still images, including 5 benign gastric ulcers, 95 with gastric cancer, and 400 normal images. Thereby we validated the CADe algorithm measuring accuracy, sensitivity, and specificity with the result of receiver operating characteristic curves (ROC) and area under curve (AUC) in addition to comparing the diagnostic performance status of four expert endoscopists, four trainees, and four beginners from two university-affiliated hospitals with CADe algorithm. After a washing-out period of over 2 weeks, endoscopists performed gastric detection on the same dataset of the 500 endoscopic images again marked by ALPHAON®. RESULTS The CADe algorithm presented high validity in detecting gastric neoplasm with accuracy (0.88, 95% CI: 0.85 to 0.91), sensitivity (0.93, 95% CI: 0.88 to 0.98), specificity (0.87, 95% CI: 0.84 to 0.90), and AUC (0.962). After a washing-out period of over 2 weeks, overall validity improved in the trainee and beginner groups with the assistance of ALPHAON®. Significant improvement was present, especially in the beginner group (accuracy 0.94 (0.93 to 0.96) p < 0.001, sensitivity 0.87 (0.82 to 0.92) p < 0.001, specificity 0.96 (0.95 to 0.97) p < 0.001). CONCLUSIONS The high validation performance state of the CADe algorithm system was verified. Also, ALPHAON® has demonstrated its potential to serve as an endoscopic educator for beginners improving and making progress in sensitivity and specificity.
Collapse
Affiliation(s)
- Hannah Lee
- Division of Gastroenterology, Department of Internal Medicine, Gachon University, Gil Medical Center, Incheon 21565, Republic of Korea
| | - Jun-Won Chung
- Division of Gastroenterology, Department of Internal Medicine, Gachon University, Gil Medical Center, Incheon 21565, Republic of Korea
| | - Sung-Cheol Yun
- Division of Biostatistics, Center for Medical Research and Information, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
| | - Sung Woo Jung
- Division of Gastroenterology, Department of Internal Medicine, Korea University College of Medicine, Ansan 15355, Republic of Korea
| | | | - Ji Hee Kim
- CAIMI Co., Ltd., Incheon 22004, Republic of Korea
| | - Boram Cha
- Division of Gastroenterology, Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon 22332, Republic of Korea
| | - Mohd Azzam Kayasseh
- Division of Gastroenterology, Dr. Sulaiman AI Habib Medical Group, Dubai Healthcare City, Dubai 51431, United Arab Emirates
| | - Kyoung Oh Kim
- Division of Gastroenterology, Department of Internal Medicine, Gachon University, Gil Medical Center, Incheon 21565, Republic of Korea
| |
Collapse
|
20
|
Jirovec E, Quixabeira DCA, Clubb JHA, Pakola SA, Kudling T, Arias V, Haybout L, Jalkanen K, Alanko T, Monberg T, Khammari A, Dreno B, Svane IM, Block MS, Adamo DA, Mäenpää J, Kistler C, Sorsa S, Hemminki O, Kanerva A, Santos JM, Cervera-Carrascon V, Hemminki A. Single intravenous administration of oncolytic adenovirus TILT-123 results in systemic tumor transduction and immune response in patients with advanced solid tumors. J Exp Clin Cancer Res 2024; 43:297. [PMID: 39506856 PMCID: PMC11539705 DOI: 10.1186/s13046-024-03219-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Accepted: 10/26/2024] [Indexed: 11/08/2024] Open
Abstract
BACKGROUND A limitation of approved oncolytic viruses is their requirement for intratumoral (i.t.) injection. TILT-123 (igrelimogene litadenorepvec, Ad5/3-E2F-D24-hTNFα-IRES-hIL-2) is a chimeric oncolytic adenovirus suitable for intravenous (i.v.) delivery due to its capsid modification and dual selectivity devices. It is armed with tumor necrosis alpha and interleukin-2 for promoting T-cell activation and lymphocyte trafficking to tumors, thereby enhancing the antitumor immune response. Here, we present the findings after a single i.v. administration of TILT-123 in three phase I dose escalation clinical trials. METHODS Patients with advanced solid tumors initially received a single i.v. dose of TILT-123 ranging from 3 × 109 to 4 × 1012 viral particles (VP). Blood was collected at baseline, 1, 16, and 192 h (7 days) post-treatment for bioavailability and serum analysis. Tumor biopsies were collected prior to treatment and 7 days post-treatment for analysis of viral presence and immunological effects. Patients did not receive any other cancer therapies during this period. RESULTS Across all three trials (TUNIMO, TUNINTIL, and PROTA), 52 total patients were treated with i.v. TILT-123. Overall, TILT-123 was found to be well-tolerated, with no dose-limiting toxicities observed. Post-treatment tumor biopsies showed expression of viral genes, presence of TILT-123 adenovirus proteins or DNA, and changes in immune cell infiltration from baseline. Increased virus dose did not lead to increased virus detection in tumors. Median overall survival was longer in patients with confirmed presence of TILT-123 in post-treatment biopsies (280 versus 190 days, p = 0.0405). CONCLUSION TILT-123 demonstrated safety and significant intratumoral immunomodulation following a single i.v. administration, warranting further investigation. TRIAL REGISTRATIONS TUNIMO-NCT04695327. Registered 4 January 2021, https://clinicaltrials.gov/study/NCT04695327 . TUNINTIL-NCT04217473. Registered 19 December 2019, https://clinicaltrials.gov/study/NCT04217473 . PROTA-NCT05271318. Registered 4 February 2022, https://clinicaltrials.gov/study/NCT05271318 .
Collapse
Affiliation(s)
- Elise Jirovec
- Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland
| | - Dafne C A Quixabeira
- Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland
- TILT Biotherapeutics Ltd, Helsinki, Finland
| | - James H A Clubb
- Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland
- TILT Biotherapeutics Ltd, Helsinki, Finland
| | - Santeri A Pakola
- Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland
| | - Tatiana Kudling
- Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland
| | - Victor Arias
- Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland
| | - Lyna Haybout
- Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland
- TILT Biotherapeutics Ltd, Helsinki, Finland
| | - Katriina Jalkanen
- Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland
| | | | - Tine Monberg
- National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Herlev, Denmark
| | - Amir Khammari
- Department of Dermatology, Nantes University, CHU Nantes, CIC1413, INSERM, CNRS, Immunology and New Concepts in ImmunoTherapy, INCIT, UMR 1302, Nantes, France
| | - Brigitte Dreno
- Nantes University, INSERM, CNRS, Immunology and New Concepts in ImmunoTherapy, INCIT, UMR 1302, Nantes, France
| | - Inge Marie Svane
- National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Herlev, Denmark
| | | | | | - Johanna Mäenpää
- Docrates Cancer Center, Helsinki, Finland
- Faculty of Medicine and Medical Technology, and Cancer Center, Tampere University and University Hospital, Tampere, Finland
| | | | - Suvi Sorsa
- TILT Biotherapeutics Ltd, Helsinki, Finland
| | - Otto Hemminki
- Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland
- Department of Urology, Helsinki University Hospital, Helsinki, Finland
| | - Anna Kanerva
- Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland
- Department of Gynecology and Obstetrics, Helsinki University Hospital, Helsinki, Finland
| | - João M Santos
- Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland
- TILT Biotherapeutics Ltd, Helsinki, Finland
| | - Victor Cervera-Carrascon
- Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland
- TILT Biotherapeutics Ltd, Helsinki, Finland
| | - Akseli Hemminki
- Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland.
- TILT Biotherapeutics Ltd, Helsinki, Finland.
- Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland.
| |
Collapse
|
21
|
Shi D, Yang Z, Cai Y, Li H, Lin L, Wu D, Zhang S, Guo Q. Research advances in the molecular classification of gastric cancer. Cell Oncol (Dordr) 2024; 47:1523-1536. [PMID: 38717722 PMCID: PMC11466988 DOI: 10.1007/s13402-024-00951-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/13/2024] [Indexed: 06/27/2024] Open
Abstract
Gastric cancer (GC) is a malignant tumor with one of the lowest five-year survival rates. Traditional first-line treatment regimens, such as platinum drugs, have limited therapeutic efficacy in treating advanced GC and significant side effects, greatly reducing patient quality of life. In contrast, trastuzumab and other immune checkpoint inhibitors, such as nivolumab and pembrolizumab, have demonstrated consistent and reliable efficacy in treating GC. Here, we discuss the intrinsic characteristics of GC from a molecular perspective and provide a comprehensive review of classification and treatment advances in the disease. Finally, we suggest several strategies based on the intrinsic molecular characteristics of GC to aid in overcoming clinical challenges in the development of precision medicine and improve patient prognosis.
Collapse
Affiliation(s)
- Dike Shi
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Jiefang Road, Hangzhou, 310009, China
| | - Zihan Yang
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Yanna Cai
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Hongbo Li
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Lele Lin
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Jiefang Road, Hangzhou, 310009, China
| | - Dan Wu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Jiefang Road, Hangzhou, 310009, China
| | - Shengyu Zhang
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
| | - Qingqu Guo
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Jiefang Road, Hangzhou, 310009, China.
| |
Collapse
|
22
|
Onwuka JU, Wuraola FO, Owoade IA, Ogunyemi YF, Di Bernardo M, Dare AJ, Mohammed TO, Sheikh M, Olasehinde O, Kingham TP, Robbins HA, Alatise OI. Delays in Presentation, Diagnosis, and Treatment Among Patients With GI Cancer in Southwest Nigeria. JCO Glob Oncol 2024; 10:e2400060. [PMID: 39418630 DOI: 10.1200/go.24.00060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 06/15/2024] [Accepted: 09/10/2024] [Indexed: 10/19/2024] Open
Abstract
PURPOSE The incidence of GI cancers is increasing in sub-Saharan African countries. We described the oncological care pathway and assessed presentation, diagnosis, and treatment intervals and delays among patients with GI cancer who presented to the Obafemi Awolowo University Teaching Hospitals Complex in Ile-Ife, Nigeria. METHODS We analyzed data from 545 patients with GI cancer in the African Research Group for Oncology (ARGO) database. We defined presentation interval as the interval between symptom onset and presentation to tertiary hospital, diagnostic interval as between presentation and diagnosis, and treatment interval as between diagnosis and initiation of treatment. We considered >3 months, >1 month, and >1 month to be presentation, diagnosis, and treatment delays, respectively. We compared lengths of intervals using Mann-Whitney U tests and logistic regression. RESULTS The most frequent cancer types were pancreatic (32%) and colorectal (28%). Most patients presented at stages III (38%) and IV (30%). The median presentation interval was 84 days (IQR, 56-191), and 49% presented after 3 months or longer. The median diagnosis and treatment intervals were 0 (IQR, 0-8) and 7 (IQR, 0-23) days, respectively. There was no relationship between age, sex, education, or distance to tertiary hospital and presentation delay, but patients with stage III to IV versus I to II had higher odds of presentation delay (odds ratio [OR], 1.68 [95% CI, 1.13 to 2.50]). Among patients with pancreatic cancer, older patients were less likely to have a diagnosis delay (OR, 0.50 [95% CI, 0.25 to 0.98]). CONCLUSION About half of patients with GI cancer in Ile-Ife, Nigeria, did not present to tertiary hospitals until more than 90 days after noticing symptoms. Efforts are warranted to improve public knowledge of GI cancer symptoms and to strengthen health systems for prompt diagnosis and referral to specialty care.
Collapse
Affiliation(s)
| | - Funmilola Olanike Wuraola
- Department of Surgery, College of Health Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria
- African Research Group for Oncology, Ile-Ife, Nigeria
| | | | | | | | - Anna J Dare
- Department of Surgery, Li Ka Shing Knowledge Institute, University of Toronto, Toronto, Canada
| | | | - Mahdi Sheikh
- Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France
| | - Olalekan Olasehinde
- Department of Surgery, College of Health Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria
| | - T Peter Kingham
- African Research Group for Oncology, Ile-Ife, Nigeria
- Department of Surgery, and Global Cancer Disparities Initiative, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Hilary A Robbins
- Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France
| | - Olusegun Isaac Alatise
- Department of Surgery, College of Health Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria
- African Research Group for Oncology, Ile-Ife, Nigeria
| |
Collapse
|
23
|
Bhardwaj P, Kim S, Koul A, Kumar Y, Changela A, Shafi J, Ijaz MF. Advanced CNN models in gastric cancer diagnosis: enhancing endoscopic image analysis with deep transfer learning. Front Oncol 2024; 14:1431912. [PMID: 39351364 PMCID: PMC11439627 DOI: 10.3389/fonc.2024.1431912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Accepted: 08/09/2024] [Indexed: 10/04/2024] Open
Abstract
Introduction The rapid advancement of science and technology has significantly expanded the capabilities of artificial intelligence, enhancing diagnostic accuracy for gastric cancer. Methods This research aims to utilize endoscopic images to identify various gastric disorders using an advanced Convolutional Neural Network (CNN) model. The Kvasir dataset, comprising images of normal Z-line, normal pylorus, ulcerative colitis, stool, and polyps, was used. Images were pre-processed and graphically analyzed to understand pixel intensity patterns, followed by feature extraction using adaptive thresholding and contour analysis for morphological values. Five deep transfer learning models-NASNetMobile, EfficientNetB5, EfficientNetB6, InceptionV3, DenseNet169-and a hybrid model combining EfficientNetB6 and DenseNet169 were evaluated using various performance metrics. Results & discussion For the complete images of gastric cancer, EfficientNetB6 computed the top performance with 99.88% accuracy on a loss of 0.049. Additionally, InceptionV3 achieved the highest testing accuracy of 97.94% for detecting normal pylorus, while EfficientNetB6 excelled in detecting ulcerative colitis and normal Z-line with accuracies of 98.8% and 97.85%, respectively. EfficientNetB5 performed best for polyps and stool with accuracies of 98.40% and 96.86%, respectively.The study demonstrates that deep transfer learning techniques can effectively predict and classify different types of gastric cancer at early stages, aiding experts in diagnosis and detection.
Collapse
Affiliation(s)
- Priya Bhardwaj
- Department of Computer Science and Engineering (CSE), Tula's Institute, Dehradun, India
| | - SeongKi Kim
- Department of Computer Science and Engineering (CSE), School of Technology, Pandit Deendayal Energy University, Gandhinagar, India
| | - Apeksha Koul
- School of Computer Science Engineering and Technology, Bennett University, Greater Noida, India
| | - Yogesh Kumar
- Department of Computer Science and Engineering (CSE), School of Technology, Pandit Deendayal Energy University, Gandhinagar, India
| | - Ankur Changela
- Department of Information and Communication Technology (ICT), School of Technology, Pandit Deendayal Energy University, Gandhinagar, India
| | - Jana Shafi
- Department of Computer Engineering and Information, College of Engineering in Wadi Alddawasir, Prince Sattam Bin Abdulaziz University, Wadi Alddawasir, Saudi Arabia
| | - Muhammad Fazal Ijaz
- School of Information Technology (IT) and Engineering, Melbourne Institute of Technology, Melbourne, VIC, Australia
| |
Collapse
|
24
|
Kotelevets SM, Chekh SA, Chukov SZ. Effectiveness of serological markers of gastric mucosal atrophy in the gastric precancer screening and in cancer prevention. World J Gastrointest Endosc 2024; 16:462-471. [PMID: 39155993 PMCID: PMC11325870 DOI: 10.4253/wjge.v16.i8.462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 06/30/2024] [Accepted: 07/25/2024] [Indexed: 08/01/2024] Open
Abstract
BACKGROUND New markers are needed to improve the effectiveness of serological screening for atrophic gastritis. AIM To develop a cost-effective method for serological screening of atrophic gastritis with a high level of sensitivity. METHODS Of the 169 patients with atrophic gastritis, selected by the visual endoscopic Kimura-Takemoto method, 165 showed histological mucosal atrophy using the updated Kimura-Takemoto method. All 169 patients were examined for postprandial levels of gastrin-17 (G17) and pepsinogen-1 (PG1) using GastroPanel® (Biohit Plc, Helsinki, Finland). RESULTS We used the histological standard of five biopsies of the gastric mucosa, in accordance with the Kimura-Takemoto classification system to assess the sensitivity of G17 in detecting gastric mucosal atrophy. We also compared the morpho-functional relationships between the detected histological degree of gastric mucosal atrophy and the serological levels of G17 and PG1, as the markers of atrophic gastritis. The sensitivity of postprandial G17 was 62.2% for serological levels of G17 (range: 0-4 pmol/L) and 100% for serological G17 (range: 0-10 pmol/L) for the detection of monofocal severe atrophic gastritis. No strong correlation was found between the levels of PG1 and degree of histological atrophy determined by the Kimura-Takemoto classification system to identify the severity of mucosal atrophy of the gastric corpus. In the presented clinical case of a 63-year-old man with multifocal atrophic gastritis, there is a pronounced positive long-term dynamics of the serological marker of atrophy - postprandial G17, after five months of rennet replacement therapy. CONCLUSION Serological screening of multifocal atrophic gastritis by assessment of postprandial G17 is a cost-effective method with high sensitivity. Postprandial G17 is an earlier marker of regression of atrophic gastritis than a morphological examination of a gastric biopsy in accordance with the Sydney system. Therefore, postprandial G17 is recommended for dynamic monitoring of atrophic gastritis after treatment.
Collapse
Affiliation(s)
- Sergey M Kotelevets
- Department of Therapy, North Caucasus State Academy, Cherkessk 369000, Karachay-Cherkess Republic, Russia
| | - Sergey A Chekh
- Department of Mathematics, North Caucasus State Academy, Cherkessk 369000, Karachay-Cherkess Republic, Russia
| | - Sergey Z Chukov
- Department of Pathological Anatomy, Stavropol State Medical University, Stavropol 355017, Russia
| |
Collapse
|
25
|
Ji XW, Lin J, Wang YT, Ruan JJ, Xu JH, Song K, Mao JS. Endoscopic detection and diagnostic strategies for minute gastric cancer: A real-world observational study. World J Gastrointest Oncol 2024; 16:3529-3538. [PMID: 39171159 PMCID: PMC11334033 DOI: 10.4251/wjgo.v16.i8.3529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Revised: 05/26/2024] [Accepted: 06/18/2024] [Indexed: 08/07/2024] Open
Abstract
BACKGROUND Minute gastric cancers (MGCs) have a favorable prognosis, but they are too small to be detected by endoscopy, with a maximum diameter ≤ 5 mm. AIM To explore endoscopic detection and diagnostic strategies for MGCs. METHODS This was a real-world observational study. The endoscopic and clinicopathological parameters of 191 MGCs between January 2015 and December 2022 were retrospectively analyzed. Endoscopic discoverable opportunity and typical neoplastic features were emphatically reviewed. RESULTS All MGCs in our study were of a single pathological type, 97.38% (186/191) of which were differentiated-type tumors. White light endoscopy (WLE) detected 84.29% (161/191) of MGCs, and the most common morphology of MGCs found by WLE was protruding. Narrow-band imaging (NBI) secondary observation detected 14.14% (27/191) of MGCs, and the most common morphology of MGCs found by NBI was flat. Another three MGCs were detected by indigo carmine third observation. If a well-demarcated border lesion exhibited a typical neoplastic color, such as yellowish-red or whitish under WLE and brownish under NBI, MGCs should be diagnosed. The proportion with high diagnostic confidence by magnifying endoscopy with NBI (ME-NBI) was significantly higher than the proportion with low diagnostic confidence and the only visible groups (94.19% > 56.92% > 32.50%, P < 0.001). CONCLUSION WLE combined with NBI and indigo carmine are helpful for detection of MGCs. A clear demarcation line combined with a typical neoplastic color using nonmagnifying observation is sufficient for diagnosis of MGCs. ME-NBI improves the endoscopic diagnostic confidence of MGCs.
Collapse
Affiliation(s)
- Xiao-Wei Ji
- Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Jie Lin
- Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Yan-Ting Wang
- Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Jing-Jing Ruan
- Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Jing-Hong Xu
- Department of Pathology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Kai Song
- Department of Pathology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Jian-Shan Mao
- Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| |
Collapse
|
26
|
Turtoi DC, Brata VD, Incze V, Ismaiel A, Dumitrascu DI, Militaru V, Munteanu MA, Botan A, Toc DA, Duse TA, Popa SL. Artificial Intelligence for the Automatic Diagnosis of Gastritis: A Systematic Review. J Clin Med 2024; 13:4818. [PMID: 39200959 PMCID: PMC11355427 DOI: 10.3390/jcm13164818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Revised: 08/11/2024] [Accepted: 08/13/2024] [Indexed: 09/02/2024] Open
Abstract
Background and Objective: Gastritis represents one of the most prevalent gastrointestinal diseases and has a multifactorial etiology, many forms of manifestation, and various symptoms. Diagnosis of gastritis is made based on clinical, endoscopic, and histological criteria, and although it is a thorough process, many cases are misdiagnosed or overlooked. This systematic review aims to provide an extensive overview of current artificial intelligence (AI) applications in gastritis diagnosis and evaluate the precision of these systems. This evaluation could highlight the role of AI as a helpful and useful tool in facilitating timely and accurate diagnoses, which in turn could improve patient outcomes. Methods: We have conducted an extensive and comprehensive literature search of PubMed, Scopus, and Web of Science, including studies published until July 2024. Results: Despite variations in study design, participant numbers and characteristics, and outcome measures, our observations suggest that implementing an AI automatic diagnostic tool into clinical practice is currently feasible, with the current systems achieving high levels of accuracy, sensitivity, and specificity. Our findings indicate that AI outperformed human experts in most studies, with multiple studies exhibiting an accuracy of over 90% for AI compared to human experts. These results highlight the significant potential of AI to enhance diagnostic accuracy and efficiency in gastroenterology. Conclusions: AI-based technologies can now automatically diagnose using images provided by gastroscopy, digital pathology, and radiology imaging. Deep learning models exhibited high levels of accuracy, sensitivity, and specificity while assessing the diagnosis, staging, and risk of neoplasia for different types of gastritis, results that are superior to those of human experts in most studies.
Collapse
Affiliation(s)
- Daria Claudia Turtoi
- Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania; (D.C.T.); (V.I.); (A.B.); (T.A.D.)
| | - Vlad Dumitru Brata
- Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania; (D.C.T.); (V.I.); (A.B.); (T.A.D.)
| | - Victor Incze
- Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania; (D.C.T.); (V.I.); (A.B.); (T.A.D.)
| | - Abdulrahman Ismaiel
- 2nd Medical Department, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania; (A.I.); (S.L.P.)
| | - Dinu Iuliu Dumitrascu
- Department of Anatomy, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania;
| | - Valentin Militaru
- Department of Internal Medicine, Clinical Municipal Hospital, 400139 Cluj-Napoca, Romania;
| | - Mihai Alexandru Munteanu
- Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, Romania;
| | - Alexandru Botan
- Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania; (D.C.T.); (V.I.); (A.B.); (T.A.D.)
| | - Dan Alexandru Toc
- Department of Microbiology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania;
| | - Traian Adrian Duse
- Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania; (D.C.T.); (V.I.); (A.B.); (T.A.D.)
| | - Stefan Lucian Popa
- 2nd Medical Department, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania; (A.I.); (S.L.P.)
| |
Collapse
|
27
|
Li H, Zhu Q, Liu L, Zou H, Gu D, Wu C, Li W. Preliminary differentiation of benign and malignant gastric wall thickening using dual-layer spectral-detector CT. Acta Radiol 2024; 65:879-888. [PMID: 39051549 DOI: 10.1177/02841851241260873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/27/2024]
Abstract
BACKGROUND Dual-layer spectral-detector computed tomography (DLCT) may have the potential to evaluate gastric wall thickening. PURPOSE To evaluate the efficacy of DLCT quantitative parameters in differentiating between benign and malignant thickening of the gastric wall. MATERIAL AND METHODS A total of 58 patients with "gastric wall thickening" who underwent multi-phase abdominal enhanced DLCT scans were included in this study. Of these patients, 33 were malignant and 25 were benign. Parameters such as iodine concentration (IC), effective atomic number (Zeff), and attenuation of the lesions were measured during the arterial phase (AP) and venous phase (VP). Binary logistic regression was employed to calculate the combined prediction probabilities. The accuracy of the DLCT parameters was assessed using receiver operating characteristic (ROC) curves. RESULTS The values of IC, nIC, Zeff, normalized Zeff, and attenuation in the AP and VP were significantly higher (all P < 0.05) in the malignant group compared to the benign group. The ROC curves revealed that the IC, Zeff, and attenuation in the VP exhibited high diagnostic performance, with area under the ROC curve (AUC) values of 0.864, 0.862, and 0.840, respectively. The new combination of these three factors and gastric wall thickness had an AUC of 0.884, and the sensitivity and specificity were determined to be 81.8% and 92.0%, respectively. CONCLUSION Spectral CT parameters, particularly the combination of gastric wall thickness, attenuation, IC, and Zeff in VP, have value in distinguishing between benign and malignant gastric wall thickening.
Collapse
Affiliation(s)
- Hongjian Li
- Department of Radiology, Shenzhen Second People's Hospital/The First Affiliated Hospital of Shenzhen University, Shenzhen, PR China
- Shantou University Medical College, Shantou, PR China
| | - Qianni Zhu
- Department of Radiology, Shenzhen Second People's Hospital/The First Affiliated Hospital of Shenzhen University, Shenzhen, PR China
| | - Linjiang Liu
- Department of Radiology, Shenzhen Second People's Hospital/The First Affiliated Hospital of Shenzhen University, Shenzhen, PR China
| | - Haijun Zou
- Department of Pharmacy, Shenzhen Second People's Hospital/The First Affiliated Hospital of Shenzhen University, Shenzhen, PR China
| | - Dayong Gu
- Department of Laboratory Medicine, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, PR China
| | - Cheng Wu
- Department of Radiology, Shenzhen Second People's Hospital/The First Affiliated Hospital of Shenzhen University, Shenzhen, PR China
| | - Weihua Li
- Department of Radiology, Shenzhen Second People's Hospital/The First Affiliated Hospital of Shenzhen University, Shenzhen, PR China
| |
Collapse
|
28
|
Deng G, Bi B, Deng H, Fan J, Huang Z, Zhang C, He Y. A nomogram predicting distant metastasis risk for gastric cancer patients with preoperative anemia: a multicenter retrospective study. World J Surg Oncol 2024; 22:206. [PMID: 39090636 PMCID: PMC11295514 DOI: 10.1186/s12957-024-03486-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Accepted: 07/17/2024] [Indexed: 08/04/2024] Open
Abstract
BACKGROUND Anemia represents a well-established risk factor for patients diagnosed with gastric cancer, and is often associated with an unfavorable prognosis. In this context, the timely prediction of distant metastasis risk in patients with anemic gastric cancer assumes paramount importance. METHODS Information of gastric cancer patients complicated with preoperative anemia in the First Affiliated Hospital of Sun Yat-sen University was collected. The cohort from the First Affiliated Hospital of Guangxi Medical University was used as an external validation set. A Nomogram was established based on the risk factors screened by univariate and multivariate logistic regression analyses. RESULTS A total of 848 gastric cancer patients with preoperative anemia were enrolled. Pyloric obstruction, carcinoma antigen 125, T stage, N stage, tumor size, and preoperative weight loss were independent predictors of distant metastasis in gastric cancer patients with anemia (p < 0.05), based on which a nomogram was constructed. The accuracy, reliability and clinical value of the nomogram were evaluated by concordance index, receiver operating characteristic curve, decision curve analysis, calibration curve and showed good stability and clinical predictive value. CONCLUSIONS Preoperative anemic gastric cancer patients, complicated with pyloric obstruction, elevated CA125, advanced T and N stage, larger tumor size, and preoperative weight loss, should be paid more attention to distant metastasis.
Collapse
Affiliation(s)
- Guofei Deng
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518000, China
| | - Bo Bi
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518000, China
| | - Huachu Deng
- Department of Gastrointestinal and Gland Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China
| | - Jingyuan Fan
- Department of Microsurgery, Orthopedic Trauma and Hand Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China
| | - Zhijian Huang
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518000, China.
- Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518000, China.
| | - Changhua Zhang
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518000, China.
- Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518000, China.
| | - Yulong He
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518000, China.
- Gastrointestinal Surgery Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China.
| |
Collapse
|
29
|
Liu L, Wang X, He Q, Yu B, Wang J, Shen H. Differential diagnosis of gastric low- and high grade dysplasia using C6orf15 protein. Ann Diagn Pathol 2024; 71:152298. [PMID: 38547762 DOI: 10.1016/j.anndiagpath.2024.152298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 03/19/2024] [Accepted: 03/20/2024] [Indexed: 06/09/2024]
Abstract
OBJECTIVE To investigate the expression of C6orf15 protein in gastric endoscopic biopsy specimens and its usage as an ancillary diagnostic biomarker in determining the grade of gastric dysplasia. METHODS We selected 102 patients with gastric endoscopic biopsy specimens from Jinling Hospital. These were divided into four groups: 22 cases of gastric mucosal benign lesions, 28 with low-grade dysplasia (LGD, intestinal-type: 21 cases,foveolar-type: 7cases), 28 with high-grade dysplasia (HGD, intestinal-type: 20 cases,foveolar-type: 8 cases), and 24 cases of gastric adenocarcinoma. We examined the expressions of C6orf15, P53, and Ki67 in 102 gastric endoscopic biopsy specimens, including 47 cases with accompanying endoscopic submucosal dissection (ESD) specimens, using immunohistochemistry. RESULTS In gastric HGD and gastric adenocarcinoma, the c6orf15 protein exhibits diffuse and strong cytoplasmic expression in tumor cells. Conversely, in gastric LGD and benign gastric mucosal lesions, the c6orf15 protein shows negative or faint yellow cytoplasmic staining. The expression rate of C6orf15 in high-grade gastric dysplasia (HGD, 93 %) and gastric adenocarcinoma (100 %) was significantly higher than in the gastric mucosal benign lesion group (0 %) and the low-grade dysplasia (LGD, 7 %) group (P < 0.001). CONCLUSION The detection of C6orf15 protein expression could serve as a valuable adjunctive diagnostic tool for distinguishing between gastric HGD, LGD, and benign lesions. The combined assessment of C6orf15, P53, and Ki67 expressions may be beneficial in determining the grade of gastric dysplasia and evaluating the risk of progression in gastric mucosal lesions in clinical practice.
Collapse
Affiliation(s)
- Leilei Liu
- Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine), Nanjing 210029, China; Department of Pathology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China
| | - Xuan Wang
- Department of Pathology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China
| | - Qibin He
- Department of Gastroenterology, Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing 211199, China
| | - Bo Yu
- Department of Pathology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China
| | - Jiandong Wang
- Department of Pathology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China.
| | - Hong Shen
- Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine), Nanjing 210029, China.
| |
Collapse
|
30
|
Wu Q, Li T, Cui Y, Jiang H, Fu Y, Jiang Q, Ding X. Unveiling clinicopathologic features and outcomes for endoscopic submucosal dissection of early gastric cancer at gastric angulus in China. BMC Cancer 2024; 24:924. [PMID: 39080615 PMCID: PMC11290107 DOI: 10.1186/s12885-024-12610-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Accepted: 07/08/2024] [Indexed: 08/02/2024] Open
Abstract
BACKGROUND With advances in endoscopic submucosal dissection (ESD) technique, an increasing number of the Chinese population are being diagnosed with early gastric cancers (EGCs) at gastric angulus. However, the relationship between gastric angulus and EGCs remains obscure. OBJECTIVES We aimed to unveil the unreported location characteristics of gastric angulus in Chinese EGC patients and the correlation between the degree of submucosal fibrosis and ESD outcomes. METHODS We retrospectively reviewed the medical records of EGC patients treated with ESD from January 2010 to March 2023. We retrospectively investigated and analyzed 740 EGC patients using multiple analyses. RESULTS Following gastric antrum (53.1%), the gastric angulus (21.8%) emerged as the second-most prevalent site for EGCs. It had highest incidence of severe submucosal fibrosis and ulceration than the other parts. Multivariate analysis showed independent associations of submucosal fibrosis at the angulus with ulceration (OR: 3.714, 95% CI: 1.041-13.249), procedure duration (OR: 1.037, 95% CI: 1.014-1.061), and perforation complication (OR: 14.611, 95% CI: 1.626-131.277) (all P < 0.05). CONCLUSIONS The gastric angulus demonstrates the highest incidence of severe submucosal fibrosis and ulceration for EGCs identified by ESD. This condition is linked to unfavorable outcomes, typically increased perforation risks and prolonged operation duration. Therefore, meticulous dissection is crucial for patients with EGCs in the gastric angulus.
Collapse
Affiliation(s)
- Qiaoyan Wu
- Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, No. 59, Liuting Street, Ningbo, Zhejiang Province, 315010, China
- Ningbo Key Laboratory of Translational Medicine Research on Gastroenterology and Hepatology, No. 59, Liuting Street, Ningbo, Zhejiang Province, 315010, China
| | - Tongyu Li
- Department of Hematology, The First Affiliated Hospital of Ningbo University, No. 59, Liuting Street, Ningbo, Zhejiang Province, 315010, China
| | - Yangyang Cui
- Department of Histopathology, Ningbo Diagnostic Pathology Center, No. 685 North Huancheng Road, Ningbo, Zhejiang Province, 315021, China
| | - Haizhong Jiang
- Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, No. 59, Liuting Street, Ningbo, Zhejiang Province, 315010, China
- Ningbo Key Laboratory of Translational Medicine Research on Gastroenterology and Hepatology, No. 59, Liuting Street, Ningbo, Zhejiang Province, 315010, China
| | - Yangbo Fu
- Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, No. 59, Liuting Street, Ningbo, Zhejiang Province, 315010, China
- Ningbo Key Laboratory of Translational Medicine Research on Gastroenterology and Hepatology, No. 59, Liuting Street, Ningbo, Zhejiang Province, 315010, China
| | - Qi Jiang
- Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, No. 59, Liuting Street, Ningbo, Zhejiang Province, 315010, China
- Ningbo Key Laboratory of Translational Medicine Research on Gastroenterology and Hepatology, No. 59, Liuting Street, Ningbo, Zhejiang Province, 315010, China
| | - Xiaoyun Ding
- Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, No. 59, Liuting Street, Ningbo, Zhejiang Province, 315010, China.
- Ningbo Key Laboratory of Translational Medicine Research on Gastroenterology and Hepatology, No. 59, Liuting Street, Ningbo, Zhejiang Province, 315010, China.
| |
Collapse
|
31
|
Lei C, Yu Y, Zhu Y, Li Y, Ma C, Ding L, Han L, Zhang H. The most recent progress of baicalein in its anti-neoplastic effects and mechanisms. Biomed Pharmacother 2024; 176:116862. [PMID: 38850656 DOI: 10.1016/j.biopha.2024.116862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 05/20/2024] [Accepted: 06/03/2024] [Indexed: 06/10/2024] Open
Abstract
Problems, such as toxic side effects and drug resistance of chemoradiotherapy, target therapy and immunotherapy accompanying the current anti-cancer treatments, have become bottlenecks limiting the clinical benefit for patients. Therefore, it is urgent to find promising anti-cancer strategies with higher efficacy and lesser side effects. Baicalein, a flavonoid component derived from the Chinese medicine scutellaria baicalensis, has been widely studied for its remarkable anti-cancer activity in multiple types of malignancies both at the molecular and cellular levels. Baicalein exerts its anti-tumor effects by inhibiting angiogenesis, invasion and migration, inducing cell apoptosis and cell cycle arrest, as well as regulating cell autophagy, metabolism, the tumor microenvironment and cancer stem cells with no obvious toxic side effects. The role of classic signaling pathways, such as PI3K/AKT/mTOR, MAPK, AMPK, Wnt/β-catenin, JAK/STAT3, MMP-2/-9, have been highlighted as the major targets for baicalein exerting its anti-malignant potential. Besides, baicalein can regulate the relevant non-coding RNAs, such as lncRNAs, miRNAs and circ-RNAs, to inhibit tumorigenesis and progression. In addition to the mentioned commonalities, baicalein shows some specific anti-tumor characteristics in some specific cancer types. Moreover, the preclinical studies of the combination of baicalein and chemoradiotherapy pave the way ahead for developing baicalein as an adjunct treatment with chemoradiotherapy. Our aim is to summary the role of baicalein in different types of cancer with its mechanisms based on in vitro and in vivo experiments, hoping providing proof for baicalein serving as an effective and safe compound for cancer treatment in clinic in the future.
Collapse
Affiliation(s)
- Chenjing Lei
- The Second Clinical Medical College of Guangzhou University of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, PR China
| | - Yaya Yu
- The Second Clinical Medical College of Guangzhou University of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, PR China.
| | - Yanjuan Zhu
- The Second Clinical Medical College of Guangzhou University of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, PR China; Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, PR China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, PR China; Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangzhou, PR China
| | - Yanan Li
- The Second Clinical Medical College of Guangzhou University of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, PR China
| | - Changju Ma
- The Second Clinical Medical College of Guangzhou University of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, PR China; Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, PR China
| | - Lina Ding
- The Second Clinical Medical College of Guangzhou University of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, PR China
| | - Ling Han
- The Second Clinical Medical College of Guangzhou University of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, PR China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, PR China.
| | - Haibo Zhang
- The Second Clinical Medical College of Guangzhou University of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, PR China; Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, PR China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, PR China; Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangzhou, PR China; State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, PR China.
| |
Collapse
|
32
|
Fu Y, Jiang J, Wu Y, Cao D, Jia Z, Zhang Y, Li D, Cui Y, Zhang Y, Cao X. Genome-wide 5-hydroxymethylcytosines in circulating cell-free DNA as noninvasive diagnostic markers for gastric cancer. Gastric Cancer 2024; 27:735-746. [PMID: 38584223 DOI: 10.1007/s10120-024-01493-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Accepted: 03/14/2024] [Indexed: 04/09/2024]
Abstract
BACKGROUND 5-Hydroxymethylcytosine-enriched gene profiles and regions show tissue-specific and tumor specific. There is a potential value to explore cell-free DNA 5-hydroxymethylcytosine feature biomarkers for early gastric cancer detection. METHODS A matched case‒control study design with 50 gastric cancer patients and 50 controls was performed to sequence the different 5-hydroxymethylcytosine modification features of cell free DNA. Significantly differential 5-hydroxymethylcytosine modification genes were identified to construct a gastric cancer diagnostic model. Data set from GEO was used as an external testing set to test the robustness of the diagnostic model. RESULTS Accounting for more than 90% of 5-hydroxymethylcytosine peaks were distributed in the gene body in both the gastric cancer and control groups. The diagnostic model was developed based on five different 5-hydroxymethylcytosine modification genes, FBXL7, PDE3A, TPO, SNTG2 and STXBP5. The model could effectively distinguish gastric cancer patients from controls in the training (AUC = 0.95, sensitivity = 88.6%, specificity = 94.3%), validation (AUC = 0.87, sensitivity = 73.3%, specificity = 93.3%) and testing (AUC = 0.90, sensitivity = 81.9%, specificity = 90.2%) sets. The risk scores of the controls from the model were significantly lower than those of gastric cancer patients in both our own data (P < 0.001) and GEO external testing data (P < 0.001), and no significant difference between different TNM stage patients (P = 0.09 and 0.66). Furthermore, there was no significant difference between the healthy control and benign gastric disease patients in the testing set from GEO (P = 0.10). CONCLUSIONS The characteristics of 5-hydroxymethylcytosine in cell free DNA are specific to gastric cancer patients, and the diagnostic model constructed by five genes' 5-hydroxymethylcytosine features could effectively identify gastric cancer patients.
Collapse
Affiliation(s)
- Yingli Fu
- Division of Clinical Epidemiology, The First Hospital of Jilin University, Changchun, China
| | - Jing Jiang
- Division of Clinical Epidemiology, The First Hospital of Jilin University, Changchun, China
| | - Yanhua Wu
- Division of Clinical Epidemiology, The First Hospital of Jilin University, Changchun, China
| | - Donghui Cao
- Division of Clinical Epidemiology, The First Hospital of Jilin University, Changchun, China
| | - Zhifang Jia
- Division of Clinical Epidemiology, The First Hospital of Jilin University, Changchun, China
| | - Yangyu Zhang
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Dongming Li
- Department of Hospital Infection Management, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Yingnan Cui
- Department of Hospital Infection Management, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Yuzheng Zhang
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
- Department of Hospital Infection Management, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Xueyuan Cao
- Department of Gastric and Colorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China.
| |
Collapse
|
33
|
Pattilachan TM, Christodoulou M, Ross S. Diagnosis to dissection: AI's role in early detection and surgical intervention for gastric cancer. J Robot Surg 2024; 18:259. [PMID: 38900376 DOI: 10.1007/s11701-024-02005-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Accepted: 06/01/2024] [Indexed: 06/21/2024]
Abstract
Gastric cancer remains a formidable health challenge worldwide; early detection and effective surgical intervention are critical for improving patient outcomes. This comprehensive review explores the evolving landscape of gastric cancer management, emphasizing the significant contributions of artificial intelligence (AI) in revolutionizing both diagnostic and therapeutic approaches. Despite advancements in the medical field, the subtle nature of early gastric cancer symptoms often leads to late-stage diagnoses, where survival rates are notably decreased. Historically, the treatment of gastric cancer has transitioned from palliative care to surgical resection, evolving further with the introduction of minimally invasive surgical (MIS) techniques. In the current era, AI has emerged as a transformative force, enhancing the precision of early gastric cancer detection through sophisticated image analysis, and supporting surgical decision-making with predictive modeling and real-time preop-, intraop-, and postoperative guidance. However, the deployment of AI in healthcare raises significant ethical, legal, and practical challenges, including the necessity for ongoing professional education and the development of standardized protocols to ensure patient safety and the effective use of AI technologies. Future directions point toward a synergistic integration of AI with clinical best practices, promising a new era of personalized, efficient, and safer gastric cancer management.
Collapse
Affiliation(s)
- Tara Menon Pattilachan
- AdventHealth Tampa, Surgery College of Medicine, Digestive Health Institute, University of Central Florida (UCF), 3000 Medical Park Drive, Suite #500, Tampa, FL, 33613, USA
| | - Maria Christodoulou
- AdventHealth Tampa, Surgery College of Medicine, Digestive Health Institute, University of Central Florida (UCF), 3000 Medical Park Drive, Suite #500, Tampa, FL, 33613, USA
| | - Sharona Ross
- AdventHealth Tampa, Surgery College of Medicine, Digestive Health Institute, University of Central Florida (UCF), 3000 Medical Park Drive, Suite #500, Tampa, FL, 33613, USA.
| |
Collapse
|
34
|
Eskandarion MR, Eskandarieh S, Shakoori Farahani A, Mahmoodzadeh H, Shahi F, Oghabian MA, Shirkoohi R. Prediction of novel biomarkers for gastric intestinal metaplasia and gastric adenocarcinoma using bioinformatics analysis. Heliyon 2024; 10:e30253. [PMID: 38737262 PMCID: PMC11088262 DOI: 10.1016/j.heliyon.2024.e30253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Revised: 04/22/2024] [Accepted: 04/23/2024] [Indexed: 05/14/2024] Open
Abstract
Background & aim The histologic and molecular changes from intestinal metaplasia (IM) to gastric cancer (GC) have not been fully characterized. The present study sought to identify potential alterations in signaling pathways in IM and GC to predict disease progression; these alterations can be considered therapeutic targets. Materials & methods Seven gene expression profiles were selected from the GEO database. Discriminate differentially expressed genes (DEGs) were analyzed by EnrichR. The STRING database, Cytoscape, Gene Expression Profiling Interactive Analysis (GEPIA), cBioPortal, NetworkAnalyst, MirWalk database, OncomiR, and bipartite miRNA‒mRNA correlation network was used for downstream analyses of selected module genes. Results Analyses revealed that extracellular matrix-receptor interactions (ITGB1, COL1A1, COL1A2, COL4A1, FN1, COL6A3, and THBS2) in GC and PPAR signaling pathway interactions (FABP1, APOC3, APOA1, HMGCS2, and PPARA and PCK1) in IM may play key roles in both the carcinogenesis and progression of underlying GC from intestinal metaplasia. IM enrichment indicated that this is closely related to digestion and absorption. The TF-hub gene regulatory network revealed that AR, TCF4, SALL4, and ESR1 were more important for hub gene expression. It was revealed that the development and prediction of GC may be affected by hsa-miR-29. It was found that PTGR1, C1orf115, CRYL1, ALDOB, and SULT1B1 were downregulated in GC and upregulated in IM. Therefore, they might have tumor suppressor activity in GC progression. Conclusion New potential biomarkers and pathways involved in GC and IM were identified that are important for the transformation of GC from IM to adenocarcinoma and can be therapeutic targets for GC.
Collapse
Affiliation(s)
| | - Sharareh Eskandarieh
- Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Abbas Shakoori Farahani
- Medical Genetics Ward, IKHC Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Habibollah Mahmoodzadeh
- Department of Surgery, Cancer Research Center, Cancer Institute, IKHC, Tehran University of Medical Sciences, Tehran, Iran
| | - Farhad Shahi
- Department of Medical Oncology, Cancer Research Center, Cancer Institute, IKHC, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Ali Oghabian
- Medical Physics Department, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Shirkoohi
- Cancer Research Center, Cancer Institute, IKHC, Tehran University of Medical Sciences, Tehran, Iran
| |
Collapse
|
35
|
Yang P, Lei H, Fu Y, Chen C, Tang L, Xia S, Guo Y, Chen G, Xie M, Yang J, Li F, Li L. Exosomal miR-151-3p in saliva: A potential non-invasive marker for gastric cancer diagnosis and prognosis modulated by Sijunzi decoction (SJZD) in mice. Heliyon 2024; 10:e29169. [PMID: 38633631 PMCID: PMC11021977 DOI: 10.1016/j.heliyon.2024.e29169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Revised: 04/01/2024] [Accepted: 04/02/2024] [Indexed: 04/19/2024] Open
Abstract
Gastric cancer (GC) is one of the most prominent malignancies that originate in the epithelial cells of the gastric mucosa and is one of the main causes of cancer-related mortality worldwide. New circulating biomarkers of exosomal RNA might have great potential for non-invasive early prognosis of GC. Sijunzi Decoction (SJZD) is a typical representative formula of the method of benefiting Qi and strengthening the spleen in Traditional Chinese Medicine (TCM). However, the effects and mechanism of SJZD in treating GC remain unclear. This study looked for biomarkers of exosomal RNA for early prognosis of GC, and explored the mechanism of SJZD in treating GC. A gastric cancer model with spleen deficiency syndrome was established in nude mice, and the curative effects of SJZD were investigated. Differentially expressed miRNAs in plasma and saliva exosomes were sequenced and analyzed. Potential target genes of these miRNAs were predicted and applied for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment annotation. Overlapping miRNAs in saliva and plasma samples were analyzed, and qRT-PCR was performed for verification. miR-151a-3p was selected, and qRT-PCR further determined that miR-151a-3p was downregulated in saliva and plasma exosomes from the SJZD group. The intersected miR-151a-3p target genes were predicted and enriched in the extrinsic apoptotic signaling pathways. SJZD significantly ameliorates gastric cancer with spleen deficiency syndrome in mouse models, and exosomal miRNAs, particularly miR-151-3p, might be modulated by SJZD in plasma and saliva. The exosomal miR-151-3p in saliva may serve as a non-invasive potential marker for gastric cancer diagnosis and prognosis.
Collapse
Affiliation(s)
- Ping Yang
- Department of Chinese and Western Integrative Medicine, Hunan Brain Hospital, Clinical Medical School of Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, China
| | - Huijun Lei
- Department of Chinese and Western Integrative Medicine, Hunan Brain Hospital, Clinical Medical School of Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
- Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
- Key Laboratory of TCM Heart and Lung Syndrome Differentiation & Medicated Diet and Dietotherapy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
| | - Yue Fu
- Department of Chinese and Western Integrative Medicine, Hunan Brain Hospital, Clinical Medical School of Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
- Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
- Key Laboratory of TCM Heart and Lung Syndrome Differentiation & Medicated Diet and Dietotherapy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
| | - Cheng Chen
- Department of Chinese and Western Integrative Medicine, Hunan Brain Hospital, Clinical Medical School of Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
- Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
- Key Laboratory of TCM Heart and Lung Syndrome Differentiation & Medicated Diet and Dietotherapy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
| | - Li Tang
- Department of Chinese and Western Integrative Medicine, Hunan Brain Hospital, Clinical Medical School of Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
| | - Shuaishuai Xia
- Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
- Key Laboratory of TCM Heart and Lung Syndrome Differentiation & Medicated Diet and Dietotherapy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
| | - Yan Guo
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, China
| | - Guangyu Chen
- Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
- Key Laboratory of TCM Heart and Lung Syndrome Differentiation & Medicated Diet and Dietotherapy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
| | - Mengzhou Xie
- Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
- Key Laboratory of TCM Heart and Lung Syndrome Differentiation & Medicated Diet and Dietotherapy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
| | - Jingjing Yang
- Community Health Service Center of Dongtang Street, Yuhua District, Changsha, Hunan, 410004, China
| | - Feng Li
- School of Dentistry, University of California, Los Angeles, Los Angeles, CA90095, United States
| | - Liang Li
- Department of Chinese and Western Integrative Medicine, Hunan Brain Hospital, Clinical Medical School of Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
- Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
- Key Laboratory of TCM Heart and Lung Syndrome Differentiation & Medicated Diet and Dietotherapy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
| |
Collapse
|
36
|
Zeng J, Song D, Li K, Cao F, Zheng Y. Deep learning model for predicting postoperative survival of patients with gastric cancer. Front Oncol 2024; 14:1329983. [PMID: 38628668 PMCID: PMC11018873 DOI: 10.3389/fonc.2024.1329983] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Accepted: 03/18/2024] [Indexed: 04/19/2024] Open
Abstract
Background Prognostic prediction for surgical treatment of gastric cancer remains valuable in clinical practice. This study aimed to develop survival models for postoperative gastric cancer patients. Methods Eleven thousand seventy-five patients from the Surveillance, Epidemiology, and End Results (SEER) database were included, and 122 patients from the Chinese database were used for external validation. The training cohort was created to create three separate models, including Cox regression, RSF, and DeepSurv, using data from the SEER database split into training and test cohorts with a 7:3 ratio. Test cohort was used to evaluate model performance using c-index, Brier scores, calibration, and the area under the curve (AUC). The new risk stratification based on the best model will be compared with the AJCC stage on the test and Chinese cohorts using decision curve analysis (DCA), the net reclassification index (NRI), and integrated discrimination improvement (IDI). Results It was discovered that the DeepSurv model predicted postoperative gastric cancer patients' overall survival (OS) with a c-index of 0.787; the area under the curve reached 0.781, 0.798, 0.868 at 1-, 3- and 5- years, respectively; the Brier score was below 0.25 at different time points; showing an advantage over the Cox and RSF models. The results are also validated in the China cohort. The calibration plots demonstrated good agreement between the DeepSurv model's forecast and actual results. The NRI values (test cohort: 0.399, 0.288, 0.267 for 1-, 3- and 5-year OS prediction; China cohort:0.399, 0.288 for 1- and 3-year OS prediction) and IDI (test cohort: 0.188, 0.169, 0.157 for 1-, 3- and 5-year OS prediction; China cohort: 0.189, 0.169 for 1- and 3-year OS prediction) indicated that the risk score stratification performed significantly better than the AJCC staging alone (P < 0.05). DCA showed that the risk score stratification was clinically useful and had better discriminative ability than the AJCC staging. Finally, an interactive native web-based prediction tool was constructed for the survival prediction of patients with postoperative gastric cancer. Conclusion In this study, a high-performance prediction model for the postoperative prognosis of gastric cancer was developed using DeepSurv, which offers essential benefits for risk stratification and prognosis prediction for each patient.
Collapse
Affiliation(s)
| | | | | | | | - Yongbin Zheng
- Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| |
Collapse
|
37
|
Deng Y, Sun Y, Wu S, Zhang T, Yang J, Liu K. Differential genetic mutations and immune cell infiltration in high- and low-risk STAD: Implications for prognosis and immunotherapy efficacy. J Cell Mol Med 2024; 28:e18174. [PMID: 38494839 PMCID: PMC10945082 DOI: 10.1111/jcmm.18174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 01/16/2024] [Accepted: 01/31/2024] [Indexed: 03/19/2024] Open
Abstract
This study investigates genetic mutations and immune cell dynamics in stomach adenocarcinoma (STAD), focusing on identifying prognostic markers and therapeutic targets. Analysis of TCGA-STAD samples revealed C > A as the most common single nucleotide variant (SNV) in both high and low-risk groups. Key mutated driver genes included TTN, TP53 and MUC16, with frame-shift mutations more prevalent in the low-risk group and missense mutations in the high-risk group. Interaction analysis of hub genes such as C1QA and CD68 showed significant correlations, impacting immune cell infiltration patterns. Using ssGSEA, we found higher immune cell infiltration (B cells, CD4+ T cells, CD8+ T cells, DC cells, NK cells) in the high-risk group, correlated with increased risk scores. xCell algorithm results indicated distinct immune infiltration levels between the groups. The study's risk scoring model proved effective in prognosis prediction and immunotherapy efficacy assessment. Key molecules like CD28, CD27 and SLAMF7 correlated significantly with risk scores, suggesting potential targets for high-risk STAD patients. Drug sensitivity analysis showed a negative correlation between risk scores and sensitivity to certain treatments, indicating potential therapeutic options for high-risk STAD patients. We also validated the carcinogenic role of RPL14 in gastric cancer through phenotypic experiments, demonstrating its influence on cancer cell proliferation, invasion and migration. Overall, this research provides crucial insights into the genetic and immune aspects of STAD, highlighting the importance of a risk scoring model for personalized treatment strategies and clinical decision-making in gastric cancer management.
Collapse
Affiliation(s)
- Yin‐yong Deng
- Department of General Surgery, West China HospitalSichuan UniversityChengduChina
- Colorectal Cancer Center, West China HospitalSichuan UniversityChengduChina
| | - Yan Sun
- Department of West China School of MedicineSichuan UniversityChengduChina
| | - Si‐jia Wu
- Department of West China School of MedicineSichuan UniversityChengduChina
| | - Tian‐ying Zhang
- Department of West China School of MedicineSichuan UniversityChengduChina
| | - Jie Yang
- Department of General Surgery, West China HospitalSichuan UniversityChengduChina
- Colorectal Cancer Center, West China HospitalSichuan UniversityChengduChina
| | - Kai Liu
- Department of General Surgery, West China HospitalSichuan UniversityChengduChina
- Department of General Surgery and Gastric Cancer Center, West China HospitalSichuan UniversityChengduChina
| |
Collapse
|
38
|
Eskandarion MR, Eskandarieh S, Tutunchi S, Shakoori Farahani A, Shirkoohi R. Investigating the role of circulating tumor cells in gastric cancer: a comprehensive systematic review and meta-analysis. Clin Exp Med 2024; 24:59. [PMID: 38554188 PMCID: PMC10981629 DOI: 10.1007/s10238-024-01310-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Accepted: 02/19/2024] [Indexed: 04/01/2024]
Abstract
Investigating the role of circulating tumor cells (CTCs) and their characteristics is still controversial in patients with gastric cancer (GC). Therefore, in this study, to provide a comprehensive review and meta-analyses of the literature on association of CTCs with gastric cancer, Scopus, Web of Science, Embase, and Medline were searched for systematic reviews and meta-analyses conducted during February 2022 using the keywords. Risk of bias, hazard ratios (HRs), and risk differences (RD) were assessed. Forty-five studies containing 3,342 GC patients from nine countries were assessed. The overall prevalence of CTC in GC was 69.37% (60.27, 77.78). The pooled result showed that increased mortality in GC patients was significantly associated with positive CTCs, poor overall survival (HR = 2.73, 95%CI 2.34-3.24, p < 0.001), and progression-free survival rate (HR = 2.78, 95%CI 2.01-3.85, p < 0.001). Subgroup analyses regarding markers, detection methods, treatment type, presence of distance metastasis, presence of lymph node metastasis, and overall risk of bias showed significant associations between the groups in terms of the incidence rates of CTCs, OS, and PFS. In addition, the results of risk differences based on sampling time showed that the use of the cell search method (RD: - 0.19, 95%CI (- 0.28, - 0.10), p < 0.001), epithelial marker (RD: - 0.12, 95%CI (- 0.25, 0.00), p 0.05) and mesenchymal markers (RD: - 0.35, 95%CI (- 0.57, - 0.13), p 0.002) before the treatment might have a higher diagnostic power to identify CTCs and also chemotherapy treatment (RD: - 0.17, 95%CI (- 0.31, - 0.03), p 0.016) could significantly reduce the number of CTCs after the treatment. We also found that the risk differences between the clinical early and advanced stages were not statistically significant (RD: - 0.10, 95%CI (- 0.23, 0.02), P 0.105). Also, in the Lauren classification, the incidence of CTC in the diffuse type (RD: - 0.19, 95%CI (- 0.37, - 0.01), P0.045) was higher than that in the intestinal type. Meta-regression analysis showed that baseline characteristics were not associated with the detection of CTCs in GC patients. According to our systematic review and meta-analysis, CTCs identification may be suggested as a diagnostic technique for gastric cancer screening, and the outcomes of CTC detection may also be utilized in the future to create personalized medicine programs.
Collapse
Affiliation(s)
| | - Sharareh Eskandarieh
- Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Sara Tutunchi
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abbas Shakoori Farahani
- Medical Genetics Ward, IKHC Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Shirkoohi
- Cancer Research Center, Cancer Institute, IKHC, Tehran University of Medical Sciences, Tehran, Iran.
| |
Collapse
|
39
|
梁 一, 赖 颖, 袁 燕, 袁 炜, 张 锡, 张 拔, 卢 志. [Screening of differentially expressed genes in gastric cancer based on GEO database and function and pathway enrichment analysis]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2024; 44:605-616. [PMID: 38597453 PMCID: PMC11006697 DOI: 10.12122/j.issn.1673-4254.2024.03.23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Indexed: 04/11/2024]
Abstract
OBJECTIVE To explore the core genes related to the diagnosis and prognosis of gastric cancer (GC) based on Gene Expression Omnibus (GEO) database and screen the molecular targets involved in the occurrence and development of GC. METHODS GC microarray data GSE118916, GSE54129 and GSE79973 were downloaded from GEO database, and the differentially expressed genes (DEGs) were screened. Enrichment analysis of the signaling pathways and molecular functions were preformed and protein-protein interaction networks (PPI) were constructed to identify the hub genes, whose expression levels and diagnostic and prognostic values were verifies based on gastric adenocarcinoma data from TCGA. The expression levels of these core genes were also detected in different GC cell lines using qRT- PCR. RESULTS Seventy-seven DEGs were identified, which encodes proteins located mainly in the extracellular matrix and basement membrane with activities of oxidoreductase and extracellular matrix receptor and ligand, involving the biological processes of digestion and hormone metabolism and the signaling pathways in retinol metabolism and gastric acid secretion. Nine hub genes were obtained, among which SPARC, TIMP1, THBS2, COL6A3 and THY1 were significantly up- regulated and TFF1, GKN1, TFF2 and PGC were significantly down-regulated in GC. The abnormal expressions of SPARC, TIMP1, THBS2, COL6A3, TFF2 and THY1 were significantly correlated with the survival time of GC patients. ROC curve analysis showed that aberrant expression of TIMP1 SPARC, THY1 and THBS2 had high diagnostic value for GC. High expressions of SPARC, TIMP1, THBS2 and COL6A3 were detected in GC tissues. In the GC cell lines, qRT- PCR revealed different expression patterns of these hub genes, but their expressions were largely consistent with those found in bioinformatics analyses. CONCLUSION SPARC, TIMP1, THBS2 and other DEGs are probably involved in GC occurrence and progression and may serve as potential candidate molecular markers for early diagnosis and prognostic evaluation of GC.
Collapse
Affiliation(s)
- 一豪 梁
- 南方医科大学第十附属医院(东莞市人民医院)检验科,广东 东莞 523059Department of Clinical Laboratory, Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Dongguan 523059, China
| | - 颖君 赖
- 南方医科大学第十附属医院(东莞市人民医院)消化内科,广东 东莞 523059Department of Gastroenterology, Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Dongguan 523059, China
| | - 燕文 袁
- 南方医科大学第十附属医院(东莞市人民医院)消化内科,广东 东莞 523059Department of Gastroenterology, Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Dongguan 523059, China
| | - 炜 袁
- 南方医科大学第十附属医院(东莞市人民医院)病理科,广东 东莞 523059Department of Pathology, Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Dongguan 523059, China
| | - 锡波 张
- 南方医科大学第十附属医院(东莞市人民医院)检验科,广东 东莞 523059Department of Clinical Laboratory, Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Dongguan 523059, China
| | - 拔山 张
- 南方医科大学第十附属医院(东莞市人民医院)检验科,广东 东莞 523059Department of Clinical Laboratory, Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Dongguan 523059, China
| | - 志锋 卢
- 南方医科大学第十附属医院(东莞市人民医院)检验科,广东 东莞 523059Department of Clinical Laboratory, Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Dongguan 523059, China
| |
Collapse
|
40
|
Zhang Z, Liao Y, Zhao P, Chen X, Liu Y, Wu J, Zuo H. Hypoxia-based critical gene biomarkers as prognostic reporters for gastric adenocarcinoma. ENVIRONMENTAL TOXICOLOGY 2024; 39:1811-1821. [PMID: 38073300 DOI: 10.1002/tox.24064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/10/2023] [Revised: 11/10/2023] [Accepted: 11/16/2023] [Indexed: 02/08/2024]
Abstract
BACKGROUND Gastric cancer is the most common malignant tumour of the digestive system, yet there is a lack of reported prognostic biomarkers for STAD patients. METHODS Transcriptomic expression data of STAD from GEO database, single cell sequencing data from OMIX gastric cancer database. Conservative molecular typing of gastric cancer was constructed using non-negative matrix factorization (NMF). The abundance of 28 immune cells in the tumour samples was assessed using ssGSEA. The R package "oncoPredict" was used to predict chemotherapy response. TIDE website for immunotherapy response prediction. Finally, single cell analysis was performed to clarify the specific type annotation of STAD cells and to analysis their spatial expression. RESULTS Hypoxia-score demonstrated excellent prognostic discrimination in TCGA gastric cancer samples. Among multiple deconvolution-based algorithms for immune infiltration, Hypoxia-score presented a general immunosuppressive efficacy across multiple datasets, as evidenced by a broad negative correlation with immune cell infiltration. By the likelihood that each group may have specific drug sensitivity to multiple chemotherapeutic and targeted agents. Results showed that high-risk scoring patients were more sensitive to Staurosporine, Sabutoclax, and AZD8055, while low-risk patients were more sensitive to Bortezomib, Dactinomycin, Docetaxel, Daporinad, Sepantronium, and bromide. In the immunotherapy cohort, the Hypoxia-score presented the ability to discriminate for immunotherapy efficacy. The distribution of Hypoxia-score in single-cell descending space was calculated using AddModuleScore and was found to be distributed across the various cell types annotated in the single-cell analysis. It is suggested that various cells in the tumour microenvironment are involved in hypoxia gene set processes to varying degrees. CONCLUSION The Hypoxia-score proves to be a valuable tool for assessing the prognosis of gastric cancer patients and guiding drug treatments, providing significant guidance for clinical diagnosis and treatment in the context of gastric cancer.
Collapse
Affiliation(s)
- Zhiya Zhang
- Department of Oncology, The Second People's Hospital of Meishan City, Meishan, Sichuan, China
| | - Yin Liao
- Department of Oncology, The Second People's Hospital of Meishan City, Meishan, Sichuan, China
| | - Peiyou Zhao
- Department of Oncology, The Second People's Hospital of Meishan City, Meishan, Sichuan, China
| | - Xinwei Chen
- Department of Oncology, The Second People's Hospital of Meishan City, Meishan, Sichuan, China
| | - Yunfei Liu
- Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich, Germany
| | - Ji Wu
- Second School of Clinical Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Hongbin Zuo
- Department of General surgery, Wuhan Jiangxia Hospital of TCM (Traditional Chinese Medicine), Wuhan, Hubei, China
| |
Collapse
|
41
|
Mahmoudzadeh-Sagheb A, Panahi M, Jami S, Moudi B, Mahmoudzadeh-Sagheb H, Heidari Z. Survivin as a potential biomarker for early diagnosis of the progression of precancerous lesions to gastric cancer. Int J Biol Markers 2024; 39:52-58. [PMID: 38055975 DOI: 10.1177/03936155231217268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/08/2023]
Abstract
BACKGROUND Gastric cancer is a common cancer developed in a carcinogenesis process from precancerous lesions including chronic gastritis, intestinal metaplasia, and dysplasia. Survivin, an inhibitor-of-apoptosis protein, is associated with the initiation and progression of gastric cancer. The present study aimed to evaluate the immunohistochemical expression patterns of survivin and its relationship with early diagnosis of gastric cancer in Iranian patients. METHODS In this retrospective case-control study, immunoexpression of survivin was investigated on sections obtained from formalin-fixed paraffin-embedded tissue blocks of 38 chronic gastritis, 32 intestinal metaplasia, 20 dysplasia, 28 gastric adenocarcinoma, and 22 controls. RESULTS Survivin immunoexpression in chronic gastritis was higher than controls, but this difference was not statistically significant (P > 0.05). However, survivin immunoexpression had a steady significant increase from control and chronic gastritis to intestinal metaplasia to dysplasia to gastric adenocarcinoma (P < 0.05). Sensitivity, specificity, and area under the curve of survivin immunohistochemical test for the diagnosis of gastric cancer were 87.5%, 74.4%, and 0.85, respectively. Males had a significantly higher survivin expression than females (P < 0.001). Also, survivin expression was significantly higher in older patients than in younger ones (P < 0.001). CONCLUSION It seems that the steady increase in survivin expression from different precancerous lesions to gastric adenocarcinoma suggests that survivin can be used as a potential biomarker for the prevention and early diagnosis of gastric cancer.
Collapse
Affiliation(s)
| | - Mehran Panahi
- Department of Histology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Setareh Jami
- Department of Histology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Bita Moudi
- Department of Histology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
- Infectious Diseases and Tropical Medicine Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Hamidreza Mahmoudzadeh-Sagheb
- Department of Histology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
- Infectious Diseases and Tropical Medicine Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Zahra Heidari
- Department of Histology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
- Infectious Diseases and Tropical Medicine Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran
| |
Collapse
|
42
|
Morgos DT, Stefani C, Miricescu D, Greabu M, Stanciu S, Nica S, Stanescu-Spinu II, Balan DG, Balcangiu-Stroescu AE, Coculescu EC, Georgescu DE, Nica RI. Targeting PI3K/AKT/mTOR and MAPK Signaling Pathways in Gastric Cancer. Int J Mol Sci 2024; 25:1848. [PMID: 38339127 PMCID: PMC10856016 DOI: 10.3390/ijms25031848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 01/26/2024] [Accepted: 01/31/2024] [Indexed: 02/12/2024] Open
Abstract
Gastric cancer (GC) is the fourth leading cause of death worldwide, with more than 1 million cases diagnosed every year. Helicobacter pylori represents the main risk factor, being responsible for 78% of the cases. Increased amounts of salt, pickled food, red meat, alcohol, smoked food, and refined sugars negatively affect the stomach wall, contributing to GC development. Several gene mutations, including PIK3CA, TP53, ARID1A, CDH1, Ras, Raf, and ERBB3 are encountered in GC pathogenesis, leading to phosphatidylinositol 3-kinase (PI3K) protein kinase B (AKT)/mammalian target of rapamycin (mTOR)-PI3K/AKT/mTOR-and mitogen-activated protein kinase (MAPK) signaling pathway activation and promoting tumoral activity. Helicobacter pylori, growth factors, cytokines, hormones, and oxidative stress also activate both pathways, enhancing GC development. In clinical trials, promising results have come from monoclonal antibodies such as trastuzumab and ramucirumab. Dual inhibitors targeting the PI3K/AKT/mTOR and MAPK signaling pathways were used in vitro studies, also with promising results. The main aim of this review is to present GC incidence and risk factors and the dysregulations of the two protein kinase complexes together with their specific inhibitors.
Collapse
Affiliation(s)
- Diana-Theodora Morgos
- Discipline of Anatomy, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Constantin Stefani
- Department I of Family Medicine and Clinical Base, “Dr. Carol Davila” Central Military Emergency University Hospital, 010825 Bucharest, Romania
| | - Daniela Miricescu
- Discipline of Biochemistry, Faculty of Dentistry, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Maria Greabu
- Discipline of Biochemistry, Faculty of Dentistry, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Silviu Stanciu
- Department of Internal Medicine and Gastroenterology, Carol Davila University of Medicine and Pharmacy, Central Military Emergency University Hospital, 010825 Bucharest, Romania;
| | - Silvia Nica
- Emergency Discipline, University Hospital of Bucharest, 050098 Bucharest, Romania;
| | - Iulia-Ioana Stanescu-Spinu
- Discipline of Physiology, Faculty of Dentistry, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (I.-I.S.-S.); (D.G.B.); (A.-E.B.-S.)
| | - Daniela Gabriela Balan
- Discipline of Physiology, Faculty of Dentistry, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (I.-I.S.-S.); (D.G.B.); (A.-E.B.-S.)
| | - Andra-Elena Balcangiu-Stroescu
- Discipline of Physiology, Faculty of Dentistry, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (I.-I.S.-S.); (D.G.B.); (A.-E.B.-S.)
| | - Elena-Claudia Coculescu
- Discipline of Oral Pathology, Faculty of Dentistry, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania;
| | - Dragos-Eugen Georgescu
- Department of General Surgery, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 50474 Bucharest, Romania;
- Department of General Surgery, “Dr. Ion Cantacuzino” Clinical Hospital, 020475 Bucharest, Romania
| | - Remus Iulian Nica
- Central Military Emergency University Hospital “Dr. Carol Davila”, 010825 Bucharest, Romania;
- Discipline of General Surgery, Faculty of Midwifery and Nursing, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
| |
Collapse
|
43
|
Gohari K, Saberi S, Esmaieli M, Tashakoripour M, Hosseini ME, Nahvijou A, Mohagheghi MA, Kazemnejad A, Mohammadi M. Development of a gastric cancer risk calculator for questionnaire-based surveillance of Iranian dyspeptic patients. BMC Gastroenterol 2024; 24:39. [PMID: 38238682 PMCID: PMC10797901 DOI: 10.1186/s12876-024-03123-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Accepted: 01/02/2024] [Indexed: 01/22/2024] Open
Abstract
BACKGROUND Gastric cancer (GC) is considered a silent killer, taking more than three quarters of a million lives annually. Therefore, prior to further costly and invasive diagnostic approaches, an initial GC risk screening is desperately in demand. METHODS In order to develop a simple risk scoring system, the demographic and lifestyle indices from 858 GC and 1132 non-ulcer dyspeptic (NUD) patients were analysed. We applied a multivariate logistic regression approach to identify the association between our target predictors and GC versus NUD. The model performance in classification was assessed by receiver operating characteristic (ROC) analysis. Our questionnaire covering 64 predictors, included known risk factors, such as demographic features, dietary habits, self-reported medical status, narcotics use, and SES indicators. RESULTS Our model segregated GC from NUD patients with the sensitivity, specificity, and accuracy rates of 85.89, 63.9, and 73.03%, respectively, which was confirmed in the development dataset (AUC equal to 86.37%, P < 0.0001). Predictors which contributed most to our GC risk calculator, based on risk scores (RS) and shared percentages (SP), included: 1) older age group [> 70 (RS:+ 241, SP:7.23), 60-70 (RS:+ 221, SP:6.60), 50-60 (RS:+ 134, SP:4.02), 2) history of gastrointestinal cancers (RS:+ 173, SP:5.19), 3) male gender (RS:+ 119, SP:3.55), 4) non-Fars ethnicity (RS:+ 89, SP:2.66), 5) illiteracy of both parents (RS:+ 78, SP:2.38), 6) rural residence (RS:+ 77, SP:2.3), and modifiable dietary behaviors (RS:+ 32 to + 53, SP:0.96 to 1.58). CONCLUSION Our developed risk calculator provides a primary screening step, prior to the subsequent costly and invasive measures. Furthermore, public awareness regarding modifiable risk predictors may encourage and promote lifestyle adjustments and healthy behaviours.
Collapse
Affiliation(s)
- Kimiya Gohari
- HPGC Research Group, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
- Department of Biostatistics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Samaneh Saberi
- HPGC Research Group, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
| | - Maryam Esmaieli
- HPGC Research Group, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
| | - Mohammad Tashakoripour
- Gastroenterology Department, Amiralam Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahmoud Eshagh Hosseini
- Gastroenterology Department, Amiralam Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Azin Nahvijou
- Cancer Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Ali Mohagheghi
- Cancer Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Anoshirvan Kazemnejad
- Department of Biostatistics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
| | - Marjan Mohammadi
- HPGC Research Group, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
| |
Collapse
|
44
|
Chen J, Sun Y, Li J, Lyu M, Yuan L, Sun J, Chen S, Hu C, Wei Q, Xu Z, Guo T, Cheng X. In-depth metaproteomics analysis of tongue coating for gastric cancer: a multicenter diagnostic research study. MICROBIOME 2024; 12:6. [PMID: 38191439 PMCID: PMC10773145 DOI: 10.1186/s40168-023-01730-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Accepted: 11/21/2023] [Indexed: 01/10/2024]
Abstract
BACKGROUND Our previous study revealed marked differences in tongue images between individuals with gastric cancer and those without gastric cancer. However, the biological mechanism of tongue images as a disease indicator remains unclear. Tongue coating, a major factor in tongue appearance, is the visible layer on the tongue dorsum that provides a vital environment for oral microorganisms. While oral microorganisms are associated with gastric and intestinal diseases, the comprehensive function profiles of oral microbiota remain incompletely understood. Metaproteomics has unique strength in revealing functional profiles of microbiota that aid in comprehending the mechanism behind specific tongue coating formation and its role as an indicator of gastric cancer. METHODS We employed pressure cycling technology and data-independent acquisition (PCT-DIA) mass spectrometry to extract and identify tongue-coating proteins from 180 gastric cancer patients and 185 non-gastric cancer patients across 5 independent research centers in China. Additionally, we investigated the temporal stability of tongue-coating proteins based on a time-series cohort. Finally, we constructed a machine learning model using the stochastic gradient boosting algorithm to identify individuals at high risk of gastric cancer based on tongue-coating microbial proteins. RESULTS We measured 1432 human-derived proteins and 13,780 microbial proteins from 345 tongue-coating samples. The abundance of tongue-coating proteins exhibited high temporal stability within an individual. Notably, we observed the downregulation of human keratins KRT2 and KRT9 on the tongue surface, as well as the downregulation of ABC transporter COG1136 in microbiota, in gastric cancer patients. This suggests a decline in the defense capacity of the lingual mucosa. Finally, we established a machine learning model that employs 50 microbial proteins of tongue coating to identify individuals at a high risk of gastric cancer, achieving an area under the curve (AUC) of 0.91 in the independent validation cohort. CONCLUSIONS We characterized the alterations in tongue-coating proteins among gastric cancer patients and constructed a gastric cancer screening model based on microbial-derived tongue-coating proteins. Tongue-coating proteins are shown as a promising indicator for identifying high-risk groups for gastric cancer. Video Abstract.
Collapse
Affiliation(s)
- Jiahui Chen
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China
- Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, China
| | - Yingying Sun
- Westlake Center for Intelligent Proteomics, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China
- School of Medicine, School of Life Sciences, Westlake University, Hangzhou, China
- Research Center for Industries of the Future, Westlake University, Hangzhou, China
| | - Jie Li
- Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China
- MOE Key Laboratory of Bioinformatics, Tsinghua University, Beijing, China
| | - Mengge Lyu
- Westlake Center for Intelligent Proteomics, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China
- School of Medicine, School of Life Sciences, Westlake University, Hangzhou, China
- Research Center for Industries of the Future, Westlake University, Hangzhou, China
| | - Li Yuan
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China
- Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, China
| | - Jiancheng Sun
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Shangqi Chen
- Department of General Surgery, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China
| | - Can Hu
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China
- Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, China
| | - Qing Wei
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China
- Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, China
| | - Zhiyuan Xu
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China.
- Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, China.
| | - Tiannan Guo
- Westlake Center for Intelligent Proteomics, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China.
- School of Medicine, School of Life Sciences, Westlake University, Hangzhou, China.
- Research Center for Industries of the Future, Westlake University, Hangzhou, China.
| | - Xiangdong Cheng
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China.
- Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, China.
| |
Collapse
|
45
|
Li JH, Zhang DY, Zhu JM, Dong L. Clinical applications and perspectives of circulating tumor DNA in gastric cancer. Cancer Cell Int 2024; 24:13. [PMID: 38184573 PMCID: PMC10770949 DOI: 10.1186/s12935-024-03209-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 01/02/2024] [Indexed: 01/08/2024] Open
Abstract
Gastric cancer remains a leading cause of cancer-related death worldwide, largely due to inadequate screening methods, late diagnosis, and limited treatment options. Liquid biopsy has emerged as a promising non-invasive approach for cancer screening and prognosis by detecting circulating tumor components like circulating tumor DNA (ctDNA) in the blood. Numerous gastric cancer-specific ctDNA biomarkers have now been identified. CtDNA analysis provides insight into genetic and epigenetic alterations in tumors, holding promise for predicting treatment response and prognosis in gastric cancer patients. This review summarizes current research on ctDNA biology and detection technologies, while highlighting clinical applications of ctDNA for gastric cancer diagnosis, prognosis, and guiding treatment decisions. Current challenges and future perspectives for ctDNA analysis are also discussed.
Collapse
Affiliation(s)
- Jing-Han Li
- Department of Gastroenterology and Hepatology and Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Dan-Ying Zhang
- Department of Gastroenterology and Hepatology and Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Ji-Min Zhu
- Department of Gastroenterology and Hepatology and Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
| | - Ling Dong
- Department of Gastroenterology and Hepatology and Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
| |
Collapse
|
46
|
Ma S, Yao Y, Xu Y, Zou M, Zhou M, Abudushalamu G, Chen Y, Cai S, Zhang C, Wu G. Comprehensive evaluation of serum circHAS2 as a novel diagnostic and prognostic biomarker for gastric cancer. Mol Carcinog 2024; 63:94-105. [PMID: 37750590 DOI: 10.1002/mc.23638] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 08/29/2023] [Accepted: 09/11/2023] [Indexed: 09/27/2023]
Abstract
The diagnosis and screening indicators for gastric cancer (GC) are not satisfactory, resulting in a large number of GC patients being missed and missing the best treatment time. Due to the special structure of circular RNAs (circRNAs), they have a more accurate and powerful ability to detect tumor occurrence. In addition, circHAS2 has been found to promote the proliferation, migration, and invasion of GC cells. Therefore, this study explored the potential of circHAS2 as a biomarker for GC. The expression level of circHAS2 in the specimens was detected by real-time fluorescent quantitative PCR. The molecular characteristics of circHAS2 were verified by agarose gel electrophoresis and Sanger sequencing. The feasibility of the circHAS2 detection method was verified by room temperature placement and repeated freezing and thawing. The diagnostic effect of circHAS2 on GC was evaluated by receiver-operating curve analysis. The correlation between circHAS2 expression level and clinical pathological parameters was analyzed using the χ2 -test. Kaplan-Meier survival curve analysis was used to analyze the survival situation of the circHAS2 high- and low-expression group. Univariate and multivariate Cox regression analysis was used to evaluate the influencing factors of prognosis in GC patients. CircHAS2 in cells can be secreted into the blood, and its expression level is significantly upregulated in the serum of patients with GC. The expression level of circHAS2 is correlated with the tissue differentiation, tumor node metastasis staging, classification, and lymph node metastasis of GC patients. CircHAS2 can effectively identify GC and even early GC. In addition, the expression levels of circHAS2 in postoperative GC patients significantly decreased and returned to normal after the second stage of chemotherapy. Finally, the circHAS2 low-expression group had better survival. The upregulated expression of circHAS2 in the serum of GC patients can effectively identify GC and early GC and can be used for effective monitoring of the prognosis of GC patients. In summary, circHAS2 can be used as an effective diagnostic and prognostic marker for GC.
Collapse
Affiliation(s)
- Shuo Ma
- Center of Clinical Laboratory Medicine, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, China
- Department of Laboratory Medicine, Medical School of Southeast University, Nanjing, Jiangsu, China
| | - Yuming Yao
- Center of Clinical Laboratory Medicine, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, China
- Department of Laboratory Medicine, Medical School of Southeast University, Nanjing, Jiangsu, China
| | - Yanhua Xu
- Department of Laboratory Medicine, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu, China
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu, China
| | - Mingyuan Zou
- Center of Clinical Laboratory Medicine, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, China
- Department of Laboratory Medicine, Medical School of Southeast University, Nanjing, Jiangsu, China
| | - Meiling Zhou
- Center of Clinical Laboratory Medicine, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, China
- Department of Laboratory Medicine, Medical School of Southeast University, Nanjing, Jiangsu, China
| | - Gulinaizhaer Abudushalamu
- Center of Clinical Laboratory Medicine, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, China
- Department of Laboratory Medicine, Medical School of Southeast University, Nanjing, Jiangsu, China
| | - Yaya Chen
- Center of Clinical Laboratory Medicine, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, China
- Department of Laboratory Medicine, Medical School of Southeast University, Nanjing, Jiangsu, China
| | - Shijie Cai
- Center of Clinical Laboratory Medicine, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, China
- Department of Laboratory Medicine, Medical School of Southeast University, Nanjing, Jiangsu, China
| | - Chen Zhang
- Center of Clinical Laboratory Medicine, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, China
| | - Guoqiu Wu
- Center of Clinical Laboratory Medicine, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, China
- Department of Laboratory Medicine, Medical School of Southeast University, Nanjing, Jiangsu, China
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Southeast University, Nanjing, Jiangsu, China
| |
Collapse
|
47
|
Pourjamal N, Shirkoohi R, Rohani E, Hashemi M. The Expression Analysis of MEST1 and GJA1 Genes in Gastric Cancer in Association with Clinicopathological Characteristics. Int J Hematol Oncol Stem Cell Res 2024; 18:83-91. [PMID: 38680714 PMCID: PMC11055422 DOI: 10.18502/ijhoscr.v18i1.14747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Accepted: 11/06/2023] [Indexed: 05/01/2024] Open
Abstract
Background: Gastric cancer is an invasive cancer, which is usually diagnosed in advanced stages. However, the markers affecting its progression, and invasion are of great importance in its diagnosis and treatment. The current research aimed to study the correlation of genes that contributed to epithelial-mesenchymal transition (EMT), Mest1, and GjA1, with some clinicopathological specifications in gastric cancer patients to better comprehend the functions of these genes in this tumor. Materials and Methods: RNA was extracted from the tumor, and normal tissues and cDNA were synthesized. Then, by designing specific primers for Gja1 and Mest1 genes, their expressions were studied by RT-PCR. The data was analyzed by GraphPad Prism 8 software. Results: Significant differences among the expressions of mentioned genes associated with clinicopathological variables of gastric cancer patients, including tumor size, grade, stage, metastasis, and lymphatic invasion were seen. Conclusion: The obtained data showed the important role of EMT-related genes, Gja1 and Mest1 in the clinical progression of the tumor. Further studies with larger sample sizes are required to confirm these genes as biomarker candidates for detecting gastric cancer.
Collapse
Affiliation(s)
- Nooshin Pourjamal
- Department of Genetics, Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran
| | - Reza Shirkoohi
- Cancer Biology Research Center, Cancer Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Elham Rohani
- Department of Genetics, Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran
| | - Mehrdad Hashemi
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| |
Collapse
|
48
|
Wang K, Thida A, Seong G, Chiu E. Perforated Gastric Cancer: A Case Report and Literature Review. Cureus 2024; 16:e51767. [PMID: 38322053 PMCID: PMC10844135 DOI: 10.7759/cureus.51767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/04/2024] [Indexed: 02/08/2024] Open
Abstract
Gastric cancer perforation is a rare but life-threatening complication of gastric cancer. We present the case of a 53-year-old male with acquired immune deficiency syndrome (AIDS) who presented to the emergency department with severe abdominal pain, was found to have an acute abdomen, and was eventually diagnosed with gastric perforation due to metastatic gastric cancer. This case highlights the challenges in diagnosing and managing perforated gastric cancer and discusses the surgical management options, including the use of laparoscopic techniques and the role of chemotherapy, particularly hyperthermic intraperitoneal chemotherapy (HIPEC).
Collapse
Affiliation(s)
- Kai Wang
- Department of Internal Medicine, St. George's University School of Medicine, New York, USA
| | - Aye Thida
- Department of Hematology and Oncology, SUNY (State University of New York) Downstate Health Sciences University/Kings County Hospital Center, New York, USA
| | - Gyuhee Seong
- Department of Medicine, SUNY (State University of New York) Downstate Health Sciences University/Kings County Hospital Center, New York, USA
| | - Edwin Chiu
- Department of Hematology and Oncology, SUNY (State University of New York) Downstate Health Sciences University/Kings County Hospital Center, New York, USA
| |
Collapse
|
49
|
Xu W, Chen S, Jiang Q, He J, Zhang F, Wang Z, Ruan C, Shi B. LUM as a novel prognostic marker and its correlation with immune infiltration in gastric cancer: a study based on immunohistochemical analysis and bioinformatics. BMC Gastroenterol 2023; 23:455. [PMID: 38129820 PMCID: PMC10740220 DOI: 10.1186/s12876-023-03075-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Accepted: 12/05/2023] [Indexed: 12/23/2023] Open
Abstract
BACKGROUND Gastric cancer (GC) is considered the sixth highly prevailing malignant neoplasm and is ranked third in terms of cancer mortality rates. To enable an early and efficient diagnosis of GC, it is important to detect the fundamental processes involved in the oncogenesis and progression of gastric malignancy. The understanding of molecular signaling pathways can facilitate the development of more effective therapeutic strategies for GC patients. METHODS The screening of genes that exhibited differential expression in early and advanced GC was performed utilizing the Gene Expression Omnibus databases (GSE3438). Based on this, the protein and protein interaction network was constructed to screen for hub genes. The resulting list of hub genes was evaluated with bioinformatic analysis and selected genes were validated the protein expression by immunohistochemistry (IHC). Finally, a competing endogenous RNA network of GC was constructed. RESULTS The three genes (ITGB1, LUM, and COL5A2) overexpressed in both early and advanced GC were identified for the first time. Their upregulation has been linked with worse overall survival (OS) time in patients with GC. Only LUM was identified as an independent risk factor for OS among GC patients by means of additional analysis. IHC results demonstrated that the expression of LUM protein was increased in GC tissue, and was positively associated with the pathological T stage. LUM expression can effectively differentiate tumorous tissue from normal tissue (area under the curve = 0.743). The area under 1-, 3-, and 5-year survival relative operating characteristics were greater than 0.6. Biological function enrichment analyses suggested that the genes related to LUM expression were involved in extracellular matrix development-related pathways and enriched in several cancer-related pathways. LUM affects the infiltration degree of cells linked to the immune system in the tumor microenvironment. In GC progression, the AC117386.2/hsa-miR-378c/LUM regulatory axis was also identified. CONCLUSION Collectively, a thorough bioinformatics analysis was carried out and an AC117386.2/hsa-miR-378c/LUM regulatory axis in the stomach adenocarcinoma dataset was detected. These findings should serve as a guide for future experimental investigations and warrant confirmation from larger studies.
Collapse
Affiliation(s)
- Wu Xu
- Department of Medical Oncology, Longyan People's Hospital, No.31 Denggao West Road, Longyan, Fujian, 364000, People's Republic of China
| | - Shasha Chen
- Department of Pathology, Longyan Second Hospital, No.8 Shuangyang West Road, Longyan, Fujian, 364000, People's Republic of China
| | - Qiuju Jiang
- Department of Pathology, Longyan Second Hospital, No.8 Shuangyang West Road, Longyan, Fujian, 364000, People's Republic of China
| | - Jinlan He
- Department of Medical Oncology, Longyan People's Hospital, No.31 Denggao West Road, Longyan, Fujian, 364000, People's Republic of China
| | - Feifei Zhang
- Department of Medical Oncology, Longyan People's Hospital, No.31 Denggao West Road, Longyan, Fujian, 364000, People's Republic of China
| | - Zhuying Wang
- Department of Medical Oncology, Longyan People's Hospital, No.31 Denggao West Road, Longyan, Fujian, 364000, People's Republic of China
| | - Caishun Ruan
- Department of Medical Oncology, Longyan People's Hospital, No.31 Denggao West Road, Longyan, Fujian, 364000, People's Republic of China
| | - Bin Shi
- Department of Medical Oncology, Longyan People's Hospital, No.31 Denggao West Road, Longyan, Fujian, 364000, People's Republic of China.
| |
Collapse
|
50
|
Boukair K, Salazar JM, Weber G, Badawi M, Ouaskit S, Simon JM. Toward the development of sensors for lung cancer: The adsorption of 1-propanol on hydrophobic zeolites. J Chem Phys 2023; 159:214712. [PMID: 38059548 DOI: 10.1063/5.0168230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Accepted: 11/07/2023] [Indexed: 12/08/2023] Open
Abstract
A healthy breath is mainly composed of water, carbon dioxide, molecular nitrogen, and oxygen and it contains many species, in small quantities, which are related to the ambient atmosphere and the metabolism. The breath of a person affected by lung cancer presents a concentration of 1-propanol higher than usual. In this context, the development of specific sensors to detect 1-propanol from breath is of high interest. The amount of propanol usually detected on the breath is of few ppb; this small quantity is a handicap for a reliable diagnostic. This limitation can be overcome if the sensor is equipped with a pre-concentrator. Our studies aim to provide an efficient material playing this role. This will contribute to the development of reliable and easy to use lung cancer detectors. For this, we investigate the properties of a few hydrophobic porous materials (chabazite, silicalite-1, and dealuminated faujasite). Hydrophobic structures are used to avoid saturation of materials by the water present in the exhaled breath. Our experimental and simulation results suggest that silicalite -1 (MFI) is the most suitable structure to be used as a pre-concentrator.
Collapse
Affiliation(s)
- K Boukair
- Laboratoire de Physique de la Matière Condensée, Hassan 2 University, Casablanca, Morroco
| | - J M Salazar
- ICB-UMR 6303 CNRS, Bourgogne Franche Comté University, Dijon, France
| | - G Weber
- ICB-UMR 6303 CNRS, Bourgogne Franche Comté University, Dijon, France
| | - M Badawi
- Laboratoire de Physique et Chimie Théoriques, University of Lorraine, Nancy, France
- Université de Lorraine, CNRS, L2CM, F-57000 Metz, France
| | - S Ouaskit
- Laboratoire de Physique de la Matière Condensée, Hassan 2 University, Casablanca, Morroco
| | - J-M Simon
- ICB-UMR 6303 CNRS, Bourgogne Franche Comté University, Dijon, France
| |
Collapse
|