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Ma FC, Zhang GL, Chi BT, Tang YL, Peng W, Liu AQ, Chen G, Gao JB, Wei DM, Ge LY. Blood-based machine learning classifiers for early diagnosis of gastric cancer via multiple miRNAs. World J Gastrointest Oncol 2025; 17:103679. [DOI: 10.4251/wjgo.v17.i4.103679] [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: 11/26/2024] [Revised: 01/16/2025] [Accepted: 02/11/2025] [Indexed: 03/25/2025] Open
Abstract
BACKGROUND Early screening methods for gastric cancer (GC) are lacking; therefore, the disease often progresses to an advanced stage when patients first start to exhibit typical symptoms. Endoscopy and pathological biopsy remain the primary diagnostic approaches, but they are invasive and not yet widely applicable for early population screening. miRNA is a highly conserved type of RNA that exists stably in plasma. Dysfunction of miRNA is linked to tumorigenesis and progression, indicating that individual miRNAs or combinations of multiple miRNAs may serve as potential biomarkers.
AIM To identify effective plasma miRNA biomarkers and investigate the clinical value of combining multiple miRNAs for early detection of GC.
METHODS Plasma samples from multiple centres were collected. Differentially expressed genes among healthy controls, early-stage GC patients, and advanced-stage GC patients were identified through small RNA sequencing (sRNA-seq) and validated via real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). A Wilcoxon signed-rank test was used to investigate the differences in miRNAs. Sequencing datasets of GC serum samples were retrieved from the Gene Expression Omnibus (GEO), ArrayExpress, and The Cancer Genome Atlas databases, and a multilayer perceptron-artificial neural network (MLP-ANN) model was constructed for the key risk miRNAs. The pROC package was used to assess the discriminatory efficacy of the model.
RESULTS Plasma samples of 107 normal, 71 early GC and 97 advanced GC patients were obtained from three centres, and serum samples of 8443 normal and 1583 GC patients were obtained from the GEO database. The sRNA-seq and RT-qPCR experiments revealed that miR-452-5p, miR-5010-5p, miR-27b-5p, miR-5189-5p, miR-552-5p and miR-199b-5p were significantly increased in early GC patients compared with healthy controls and in advanced GC patients compared with early GC patients (P < 0.05). An MLP-ANN model was constructed for the six key miRNAs. The area under the curve (AUC) within the training cohort was 0.983 [95% confidence interval (CI): 0.980–0.986]. In the two validation cohorts, the AUCs were 0.995 (95%CI: 0.987 to nearly 1.000) and 0.979 (95%CI: 0.972–0.986), respectively.
CONCLUSION Potential miRNA biomarkers, including miR-452-5p, miR-5010-5p, miR-27b-5p, miR-5189-5p, miR-552-5p and miR-199b-5p, were identified. A GC classifier based on these miRNAs was developed, benefiting early detection and population screening.
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Affiliation(s)
- Fu-Chao Ma
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Guan-Lan Zhang
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Bang-Teng Chi
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Yu-Lu Tang
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Wei Peng
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Ai-Qun Liu
- Department of Endoscopy, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Gang Chen
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Jin-Biao Gao
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Dan-Ming Wei
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Lian-Ying Ge
- Department of Endoscopy, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
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Lin Z, Sun W, Zhao X, Chen Y, Loomes KM, Li H, Hui HX, Wu D. Heterologous expression, purification and generation of specific antibodies for Annexin A8. Protein Expr Purif 2025; 227:106644. [PMID: 39674528 DOI: 10.1016/j.pep.2024.106644] [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: 08/13/2024] [Revised: 12/02/2024] [Accepted: 12/08/2024] [Indexed: 12/16/2024]
Abstract
Annexin A8 (ANXA8) is a member of the Annexin gene family, with high levels of its mRNA and protein observed in various tumor tissues, making it a potential tumor biomarker. In this study, we developed an enzyme-linked immunosorbent assay (ELISA) to specifically detect the presence and accurately determine the concentration of ANXA8. To this end, we expressed a series of proteins using both Pichia pastoris and Escherichia coli expression systems. Particularly, human ANXA8 expressed in Pichia pastoris was used as the antigen and for antibody screening, while human ANXA2 and ANXA5 expressed in Pichia pastoris and murine ANXA8 expressed in E. coli BL21 (DE3) were used as counter screens to eliminate cross-reactive antibodies and to select antibodies that show specificity to ANXA8 from both human and mouse. Through research efforts with production and purification of recombinant proteins, immunization, specificity screening and selection of epitope pairing, two specific monoclonal antibodies, E9 and B7, apparently targeting different epitopes of ANXA8, were obtained. The specificity of the antibody pair was checked against recombinant human ANXA2 and ANXA5 with ANXA8 as the positive control. Western Blot and Sandwich ELISA demonstrate superb sensitivity and specificity with a detection limit of about 0.065 ng/mL for the latter. In summary, this study provides an experimental tool for the quantitative determination of ANXA8 concentration and a potential tumor biomarker to monitor disease progression.
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Affiliation(s)
- Zexin Lin
- Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
| | - Wei Sun
- Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; China-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou, China
| | - Xuemei Zhao
- School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China
| | - Yang Chen
- Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; China-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou, China
| | - Kerry M Loomes
- School of Biological Sciences & Maurice Wilkins Centre, University of Auckland, Auckland, New Zealand
| | - Hongbo Li
- Hunan Provincial Key Laboratory for Synthetic Biology of Traditional Chinese Medicine, School of Pharmaceutical Sciences, Hunan University of Medicine, Huaihua, Hunan, China.
| | - Hannah Xiaoyan Hui
- School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China; CUHK-GIBH CAS Joint Research Laboratory on Stem Cell and Regenerative Medicine, SBS, CUHK, China.
| | - Donghai Wu
- Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; China-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou, China.
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3
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Fu B, Luo D, Li C, Feng Y, Liang W. Advances in micro-/nanorobots for cancer diagnosis and treatment: propulsion mechanisms, early detection, and cancer therapy. Front Chem 2025; 13:1537917. [PMID: 39981265 PMCID: PMC11839623 DOI: 10.3389/fchem.2025.1537917] [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: 12/02/2024] [Accepted: 01/20/2025] [Indexed: 02/22/2025] Open
Abstract
In recent years, medical micro-/nanorobots (MNRs) have emerged as a promising technology for diagnosing and treating malignant tumors. MNRs enable precise, targeted actions at the cellular level, addressing several limitations of conventional cancer diagnosis and treatment, such as insufficient early diagnosis, nonspecific drug delivery, and chemoresistance. This review provides an in-depth discussion of the propulsion mechanisms of MNRs, including chemical fuels, external fields (light, ultrasound, magnetism), biological propulsion, and hybrid methods, highlighting their respective advantages and limitations. Additionally, we discuss novel approaches for tumor diagnosis, precision surgery, and drug delivery, emphasizing their potential clinical applications. Despite significant advancements, challenges such as biocompatibility, propulsion efficiency, and clinical translation persist. This review examines the current state of MNR applications and outlines future directions for their development, with the aim of enhancing their diagnostic and therapeutic efficacy and facilitating their integration into clinical practice.
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Affiliation(s)
- Baiyang Fu
- Department of Breast Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Dan Luo
- College of Automotive and Mechanical Engineering, Harbin Cambridge University, Harbin, China
| | - Chao Li
- Department of Rheumatology and Immunology, Daqing Oilfield General Hospital, Daqing, China
| | - Yiwen Feng
- Key Laboratory for Micro/Nano Technology and System of Liaoning Province, Dalian University of Technology, Dalian, China
| | - Wenlong Liang
- Department of Breast Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
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Su LT, Yang ZQ, Peng HP, Liu AL. A Dual Nano-Signal Probe-Based Electrochemical Immunosensor for the Simultaneous Detection of Two Biomarkers in Gastric Cancer. BIOSENSORS 2025; 15:80. [PMID: 39996982 PMCID: PMC11853661 DOI: 10.3390/bios15020080] [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: 11/04/2024] [Revised: 01/28/2025] [Accepted: 01/29/2025] [Indexed: 02/26/2025]
Abstract
Detecting multiple tumor markers is of great importance. It helps in early cancer detection, accurate diagnosis, and monitoring treatment. In this work, gold nanoparticles-toluidine blue-graphene oxide (AuNPs-TB-GO) and gold nanoparticles-carboxyl ferrocene-tungsten disulfide (AuNPs-FMC-WS2) nanocomposites were prepared for labeling Carcinoembryonic antigen (CEA) antibody and Carbohydrate antigen 72-4 (CA72-4) antibody, respectively, and used as two kinds of probes with different electrochemical signals. With the excellent magnetic performance of biotin immune magnetic beads (IMBs), the biofunctional IMBs were firmly deposited on the magnetic glassy carbon electrode (MGCE) surface by applying a constant magnetic field, and then the CEA and CA72-4 antibody were immobilized on the IMBs by the avidin-biotin conjugation. The assay was based on the change in the detection peak current. Under the optimum experimental conditions, the linear range of detection of CEA is of the two-component immunosensor is from 0.01 to 120 ng/mL, with a low detection limit of 0.003 ng/mL, and the linear range of detection of CA72-4 is from 0.05 to 35 U/mL, with a detection limit of 0.016 U/mL. The results showed that the proposed immunosensor enabled simultaneous monitoring of CEA and CA72-4 and exhibited good reproducibility, excellent high selectivity, and sensitivity. In particular, the proposed multiplexed immunoassay approach does not require sophisticated fabrication and is well-suited for high-throughput biosensing and application to other areas.
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Affiliation(s)
- Li-Ting Su
- Quanzhou Medical College, Quanzhou 362000, China;
- The School of Pharmacy, Fujian Medical University, Fuzhou 350122, China;
| | - Zhen-Qing Yang
- The School of Pharmacy, Fujian Medical University, Fuzhou 350122, China;
| | - Hua-Ping Peng
- The School of Pharmacy, Fujian Medical University, Fuzhou 350122, China;
| | - Ai-Lin Liu
- The School of Pharmacy, Fujian Medical University, Fuzhou 350122, China;
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Xie W, Hu C, Liu H, Wu Z, Luo B, Wu X, Tuo C, Deng Z, Liang H, Liu Y, Gong W. Dual-positive gastric cancer: an extremely malignant subtype of gastric cancer with high serum alpha-fetoprotein and carcinoembryonic antigen concentrations. Front Oncol 2025; 14:1514069. [PMID: 39902132 PMCID: PMC11788079 DOI: 10.3389/fonc.2024.1514069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2024] [Accepted: 12/16/2024] [Indexed: 02/05/2025] Open
Abstract
Background Alpha-fetoprotein-producing gastric cancer (AFPGC) is a highly malignant subtype of gastric cancer, but solely alpha-fetoprotein may fail to accurately predict the prognosis. Although the utilization of multi tumor markers could improve stratified patient management, such research in AFPGC is still blank. This study seeks to evaluate whether combining multiple tumor markers can enhance risk stratification and identify AFPGC subtypes with poor prognosis. Methods We first screened for patients with elevated serum CEA levels within the AFPGC cohort and evaluated their prognosis. Tumor characteristics and overall health conditions were analyzed to identify factors contributing to CEA elevation. Finally, the treatment responses of this group to different treatment modalities were also reviewed. Results Approximately 45% of gastric cancer patients with elevated serum AFP also show increased CEA levels, classifying them as the dual-positive gastric cancer (DPGC) subgroup. These patients exhibit significantly shorter overall survival, heightened metastasis risk, and are more susceptible to systemic inflammation, immune response dysregulation, malnutrition, and cancer-related thrombosis. The elevation in serum CEA levels may indicate gastric cancer liver metastasis and increased neutrophils. While surgery is optimal for AFPGC, DPGC patients benefit significantly from immunotherapy combined with chemotherapy. Conclusions In AFPGC, combining serum AFP and CEA offers a more accurate prognosis. The poor prognosis in DPGC may be associated with aggressive local properties and systemic complications. Liver metastases and increased neutrophils are associated with increased serum CEA in AFPGC. Immunochemotherapy is a viable option for DPGC patients who cannot undergo surgery.
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Affiliation(s)
- Weixun Xie
- Department of Surgery, Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China
| | - Chengyu Hu
- Department of Surgery, Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China
| | - Hongming Liu
- Department of Surgery, Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China
| | - Zelai Wu
- Department of Surgery, Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China
| | - Bixian Luo
- Department of Surgery, Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China
| | - Xiaoying Wu
- Department of Surgery, Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China
- Department of General Surgery, Tongde Hospital of Zhejiang Province, Hangzhou, China
| | - Chuanlei Tuo
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive Cancer, Tianjin, China
| | - Ziyin Deng
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive Cancer, Tianjin, China
| | - Han Liang
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive Cancer, Tianjin, China
| | - Yong Liu
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive Cancer, Tianjin, China
| | - Weihua Gong
- Department of Surgery, Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, China
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Gorjizadeh N, Arani AS, Yazdi SAM, Biglari M, Bahar M. Distinct clinical phenotypes in gastric pathologies: a cluster analysis of demographic and biomarker profiles in a diverse patient population. J Gastrointest Surg 2025; 29:101956. [PMID: 39793959 DOI: 10.1016/j.gassur.2025.101956] [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: 09/24/2024] [Revised: 12/19/2024] [Accepted: 01/05/2025] [Indexed: 01/13/2025]
Abstract
BACKGROUND Understanding the heterogeneity of a population at risk is an important step in the early detection of gastric cancer. This study aimed to cluster demographic, hematologic, and biochemical markers of gastric cancer in a heterogeneous sample of patients. METHODS Data of 695 adult patients (50.0% women) who were diagnosed with histologically confirmed gastric cancer or benign gastric disease or identified as healthy individuals (December 2018 to August 2019; Hangzhou, China) were analyzed. A hierarchical clustering was performed using a factorial analysis of mixed data. To assess the clustering scheme, a machine-learning classification model was developed using the Extreme Gradient Boosting algorithm and subsequently ranked the variables for differentiating patient phenotypes. RESULTS Of note, 3 clusters were identified using patient characteristics. The classification model demonstrated high performance (multiclass area under the curve = 0.921) in recognizing the clusters. The top 5 important variables in differentiating the clusters were sex (male/female), hemoglobin, albumin, creatinine, and high-density lipoprotein (all analysis of variance P <.001) in decreasing order of importance. The prevalence rates of gastric cancer in clusters I, II, and III were 95.8%, 53.8%, and 34%, respectively (χ2(2) = 164.050; P <.001). Cluster I (n = 167) predominantly had an inflammatory profile, cluster II (n = 240) had metabolic disturbances, and cluster III (n = 288) had a relatively favorable metabolic and inflammatory profile. CONCLUSION There were distinct clinical phenotypes in the population, each with varying prevalence of gastric cancer. A combination of routine clinical data outperformed carbohydrate or carcinoembryonic antigens in capturing the heterogeneity of the population regarding gastric pathologies.
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Affiliation(s)
- Neda Gorjizadeh
- Department of Internal Medicine, Sina University Hospital, Tehran University of Medical Sciences, Tehran, Iran.
| | - Ali Sheibani Arani
- Department of Internal Medicine, Shahid Beheshti University Hospital, Kashan University of Medical Sciences, Kashan, Iran
| | - Seyed Amir Miratashi Yazdi
- Department of Surgery, Sina University Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Biglari
- Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran
| | - Massih Bahar
- Department of Medical Genetics, Familial and Hereditary Cancers Institute, Tehran, Iran
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Hashemi F, Tajik F, Saeednejad Zanjani L, Dehghan Manshadi M, Safaei S, Babaheidarian P, Fattahi F, Ghods R, Madjd Z. Clinical significance of Talin-1 and HER-2 status in different types of gastric carcinoma. Biomarkers 2024; 29:539-556. [PMID: 39466840 DOI: 10.1080/1354750x.2024.2423270] [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: 07/11/2024] [Accepted: 10/25/2024] [Indexed: 10/30/2024]
Abstract
BACKGROUND Talin-1 (TLN1) is crucial in cell migration, metastasis, and cancer development. This study evaluated Talin-1 expression and its clinical significance in gastric cancer (GC), along with human epidermal growth factor receptor-2 (HER-2) expression and its correlation with Talin-1. METHODS Bioinformatics analysis assessed the potential prognostic value of Talin-1 and HER-2 in GC patients. The study included 223 GC patients (Signet Ring Cells and Intestinal subtypes) and 29 non-malignant tissue samples. Immunohistochemistry (IHC) on tissue microarray slides evaluated Talin-1 and HER-2 expression and clinical significance. Receiver operating characteristic (ROC) curves assessed their diagnostic value. RESULTS Bioinformatics identified Talin-1 as a potential prognostic factor and HER-2 as an oncogene in GC. Talin-1 and HER-2 expression increased in SRC-type GC samples compared to non-malignant tissues. High cytoplasmic Talin-1 expression inversely correlated with tumor expansion and invasion in SRC-type GC. Increased HER-2 expression positively correlated with metastasis. ROC curves showed significant diagnostic values for both proteins. CONCLUSIONS Higher cytoplasmic Talin-1 expression is associated with less invasive tumor behavior, while increased membranous HER-2 expression is associated with metastasis in SRC-type GC. These findings suggest potential use in assessing diagnosis and screening high-risk cancer patients, particularly those with SRC-type GC.
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Affiliation(s)
- Farideh Hashemi
- Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran Iran
| | - Fatemeh Tajik
- Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran
| | | | - Masoumeh Dehghan Manshadi
- Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran Iran
| | - Sadegh Safaei
- Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran Iran
| | | | - Fahimeh Fattahi
- Clinical Research Development Unit of Ayatollah-Khansari Hospital, Arak University of Medical Sciences, Arak, Iran
| | - Roya Ghods
- Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran Iran
| | - Zahra Madjd
- Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran Iran
- Department of Pathology, Iran University of Medical Sciences, Tehran, Iran
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Pu J, Yan X, Zhang H. The potential of circular RNAs as biomarkers and therapeutic targets for gastric cancer: A comprehensive review. J Adv Res 2024:S2090-1232(24)00551-4. [PMID: 39617262 DOI: 10.1016/j.jare.2024.11.032] [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: 07/11/2024] [Revised: 11/22/2024] [Accepted: 11/26/2024] [Indexed: 12/08/2024] Open
Abstract
BACKGROUND Gastric cancer (GC) is a global health concern, contributing significantly to cancer-related mortality rates. Early detection is vital for improving patient outcomes. Recently, circular RNAs (circRNAs) have emerged as crucial players in the development and progression of various cancers, including GC. AIM This comprehensive review underscores the promising potential of circRNAs as innovative biomarkers for the early diagnosis of GC, as well as their possible utility as therapeutic targets for this life-threatening disease. Specifically, the review focuses on recent findings, mechanistic insights, and clinical applications of circRNAs in GC. KEY SCIENTIFIC CONCEPTS OF REVIEW Dysregulation of circRNAs has been consistently observed in GC tissues, offering potential diagnostic value due to their stability in bodily fluids such as blood and urine. For instance, circPTPN22 and hsa_circ_000200. Furthermore, the expression levels of circRNAs such as circCUL2, hsa_circ_0000705 and circSHKBP1 have shown strong associations with critical clinical features of GC, including diagnosis, prognosis, tumor size, lymph node metastasis, tumor-node-metastasis (TNM) stage, and treatment response. Additionally, circRNAs such as circBGN, circLMO7, and circMAP7D1 have shown interactions with specific microRNAs (miRNAs), proteins, and other molecules that play key roles in development and progression of GC. This further highlighting their potential as therapeutic targets. Despite their potential, several challenges need to be addressed to effectively apply circRNAs as GC biomarkers. These include standardizing detection methods, establishing cutoff values for diagnostic accuracy, and validating findings in larger patient cohorts. Moreover, the functional mechanisms by which circRNAs contribute to GC pathogenesis and therapeutic resistance warrant further investigation. Advances in circRNAs research could provide valuable insights into the early detection and targeted treatment of GC, ultimately improving patient outcomes.
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Affiliation(s)
- Junlin Pu
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Xiuli Yan
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
| | - Hui Zhang
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
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9
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Li J, Xie B, Wang H, Wang Q, Wu Y. Investigating MATN3 and ASPN as novel drivers of gastric cancer progression via EMT pathways. Hum Mol Genet 2024; 33:2035-2050. [PMID: 39301785 DOI: 10.1093/hmg/ddae129] [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: 06/24/2024] [Revised: 08/09/2024] [Accepted: 08/24/2024] [Indexed: 09/22/2024] Open
Abstract
Gastric cancer (GC) is a leading cause of cancer-related deaths globally, necessitating the identification of novel therapeutic targets. This study investigates the roles of MATN3 and ASPN in GC progression via the epithelial-mesenchymal transition (EMT) pathway. Analysis of the Cancer Genome Atlas-Stomach Adenocarcinoma (TCGA-STAD) dataset revealed that both MATN3 and ASPN are significantly upregulated in GC tissues and correlate with poor patient survival. Protein-protein interaction and co-expression analyses confirmed a direct interaction between MATN3 and ASPN, suggesting their synergistic role in EMT activation. Functional assays demonstrated that MATN3 promotes GC cell proliferation, migration, and invasion, while its knockdown inhibits these malignant behaviors and induces apoptosis. ASPN overexpression further amplified these oncogenic effects. In vivo, studies in a mouse model corroborated that co-overexpression of MATN3 and ASPN enhances tumor growth and metastasis. These findings highlight the MATN3-ASPN axis as a potential therapeutic target in GC, offering new insights into the molecular mechanisms driving GC progression.
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Affiliation(s)
- Jing Li
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Soochow University, No. 1055, Sanxiang Road, Suzhou 215004, Jiangsu Province, China
- Department of Oncological Surgery, The First Affiliated Hospital of Bengbu Medical University, No. 287, Changhuai Road, Longzihu District, Bengbu 233004, Anhui Province, China
| | - Bo Xie
- Department of Oncological Surgery, The First Affiliated Hospital of Bengbu Medical University, No. 287, Changhuai Road, Longzihu District, Bengbu 233004, Anhui Province, China
| | - Hu Wang
- Department of Oncological Surgery, The First Affiliated Hospital of Bengbu Medical University, No. 287, Changhuai Road, Longzihu District, Bengbu 233004, Anhui Province, China
| | - QingKang Wang
- Department of Oncological Surgery, The First Affiliated Hospital of Bengbu Medical University, No. 287, Changhuai Road, Longzihu District, Bengbu 233004, Anhui Province, China
| | - YongYou Wu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Soochow University, No. 1055, Sanxiang Road, Suzhou 215004, Jiangsu Province, China
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10
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Li C, Xing X, Huang S, Zhu T, Yan B. Circular RNA LDLRAD3 promotes gastric cancer progression by upregulating COL4A5 through sponging miR-h37. J Chin Med Assoc 2024; 87:1018-1028. [PMID: 39161132 DOI: 10.1097/jcma.0000000000001153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/21/2024] Open
Abstract
BACKGROUND Circular RNAs play an important role in the development of gastric cancer (GC). circ-low-density lipoprotein receptor class A domain containing 3 (LDLRAD3) has been confirmed to be related to GC progression. miR-137 is also a suppressor in GC. However, the impact of the interaction between circ-LDLRAD3 and miR-137 on the progression of GC remains unclear at present. METHODS The study identified expression level differences of circ-LDLRAD3, miR-137, and COL4A5 in GC pathological specimens compared to normal tissue samples. Furthermore, through in vitro experiments, including flow cytometry, cell counting kit-8 (CCK-8) assays, wound healing, Western blotting, and colony formation assays, we further explored the molecular regulatory mechanisms by which these factors promote the progression of GC. RESULTS In this study, circ-LDLRAD3 was confirmed to have higher expression, and miR-137 had lower expression in GC tissues and cell lines. circ-LDLRAD3 knockdown and miR-137 overexpression promoted apoptosis and inhibited proliferation, migration, and invasion in GC cell lines. Further experiments validated that COL4A5 had a positive relationship with GC and that circ-LDLRAD3 promoted the expression of COL4A5. circ-LDLRAD3 could be sponged and inhibited by miR-137 in GC cells. As a result, the promotional effect of circ-LDLRAD3 on COL4A5 was counteracted by miR-137. CONCLUSION Our study showed that the knockdown of circ-LDLRAD3 suppressed the development of GC by regulating the miR-137/COL4A5 axis.
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Affiliation(s)
- Chenghui Li
- Department of General Surgery, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, China
| | - Xiao Xing
- Department of General Surgery, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, China
| | - Sinian Huang
- Department of Pathology Surgery, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, China
| | - Ting Zhu
- Department of Pathology Surgery, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, China
| | - Bin Yan
- Department of General Surgery, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, China
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11
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李 英, 包 寒, 张 森, 孟 靖. [Recent advances in responsive isolation, release and clinical application of circulating tumor cells]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2024; 44:1637-1644. [PMID: 39505330 PMCID: PMC11744074 DOI: 10.12122/j.issn.1673-4254.2024.09.02] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Indexed: 11/08/2024]
Abstract
Circulating tumor cells (CTCs) are cells that dissociate from the tumor tissue and enter the lymphatic system or bloodstream with close association with tumor metastasis and recurrence. CTCs contain complete pathological information, which can be extracted by isolation, enrichment, and analysis of the CTCs to guide cancer diagnosis and treatment, thereby significantly improving the monitoring efficiency and prognosis of cancer. Compared with tissue biopsy, liquid biopsy with CTCs as a biomarker enables specific and dynamic detection of tumor growth with a less painful experience. For detection of CTCs, the cells must be captured from body fluids, followed then by their release and enrichment. This review summaries the latest research progress in responsive isolation of CTCs (e.g. with light, dielectrophoresis, acoustophoresis and magnetophoresis), chemical isolation (specific molecules and topological structure) and responsive release (e.g., light, electric, thermal, pH, enzyme responsiveness, and substrates break). Responsive isolation utilizes the differences in physical properties between CTCs and blood cells, while chemical isolation utilizes specific recognition mechanisms to capture the CTCs. These techniques result in low cell damage with a high specificity to facilitate further analysis. Currently, CTC detection has been applied for early diagnosis and prognostic assessment of multiple cancers including lung cancer, liver cancer, colorectal cancer, and prostate cancer.
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Affiliation(s)
- 英博 李
- />中国科学院理化技术研究所仿生材料与界面科学重点实验室，北京 100190Key Laboratory of Bio-inspired Materials and Interfacial Science, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences
| | - 寒 包
- />中国科学院理化技术研究所仿生材料与界面科学重点实验室，北京 100190Key Laboratory of Bio-inspired Materials and Interfacial Science, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences
| | - 森 张
- />中国科学院理化技术研究所仿生材料与界面科学重点实验室，北京 100190Key Laboratory of Bio-inspired Materials and Interfacial Science, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences
| | - 靖昕 孟
- />中国科学院理化技术研究所仿生材料与界面科学重点实验室，北京 100190Key Laboratory of Bio-inspired Materials and Interfacial Science, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences
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12
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Xu B, Shi Y, Yuan C, Wang Z, Chen Q, Wang C, Chai J. Integrated gene-metabolite association network analysis reveals key metabolic pathways in gastric adenocarcinoma. Heliyon 2024; 10:e37156. [PMID: 39319160 PMCID: PMC11419903 DOI: 10.1016/j.heliyon.2024.e37156] [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: 03/05/2024] [Revised: 07/22/2024] [Accepted: 08/28/2024] [Indexed: 09/26/2024] Open
Abstract
Gastric adenocarcinoma is one of the most death cause cancers worldwide. Metabolomics is an effective approach for investigating the occurrence and progression of cancer and detecting prognostic biomarkers by studying the profiles of small bioactive molecules. To fully decipher the functional roles of the disrupted metabolites that modulate the cellular mechanism of gastric cancer, integrated gene-metabolite association network methods are critical to map the associations between metabolites and genes. In this study, we constructed a knowledge-based gene-metabolite association network of gastric cancer using the dysregulated metabolites and genes between gastric cancer patients and control group. The topological pathway analysis and gene-protein-metabolite-disease association analysis revealed four key gene-metabolite pathways which include eleven metabolites associated with modulated genes. The integrated gene-metabolite association network enables mechanistic investigation and provides a comprehensive overview regarding the investigation of molecular mechanisms of gastric cancer, which facilitates the in-depth understanding of metabolic biomarker roles in gastric cancer.
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Affiliation(s)
- Botao Xu
- Department of Gastrointestinal Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, China
| | - Yuying Shi
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China
- National Institute of Health Data Science of China, Shandong University, Jinan, 250000, China
- National Science Library (Chengdu), Chinese Academy of Sciences, Chengdu, 610299, China
| | - Chuang Yuan
- Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Peking University, Beijing, 100191, China
| | - Zhe Wang
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, Shandong, China
| | - Qitao Chen
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China
- National Institute of Health Data Science of China, Shandong University, Jinan, 250000, China
| | - Cheng Wang
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China
- National Institute of Health Data Science of China, Shandong University, Jinan, 250000, China
| | - Jie Chai
- Department of Gastrointestinal Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, China
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13
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Peng B, Lin Y, Yi G, Lin M, Xiao Y, Qiu Y, Yao W, Zhou X, Liu Z. Comprehensive landscape of m6A regulator-related gene patterns and tumor microenvironment infiltration characterization in gastric cancer. Sci Rep 2024; 14:16404. [PMID: 39013954 PMCID: PMC11252343 DOI: 10.1038/s41598-024-66744-0] [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: 02/22/2024] [Accepted: 07/03/2024] [Indexed: 07/18/2024] Open
Abstract
The epigenetic regulation of N6-methyladenosine (m6A) has attracted considerable interest in tumor research, but the potential roles of m6A regulator-related genes, remain largely unknown within the context of gastric cancer (GC) and tumor microenvironment (TME). Here, a comprehensive strategy of data mining and computational biology utilizing multiple datasets based on 28 m6A regulators (including novel anti-readers) was employed to identify m6A regulator-related genes and patterns and elucidate their underlying mechanisms in GC. Subsequently, a scoring system was constructed to evaluate individual prognosis and immunotherapy response. Three distinct m6A regulator-related patterns were identified through the unsupervised clustering of 56 m6A regulator-related genes (all significantly associated with GC prognosis). TME characterization revealed that these patterns highly corresponded to immune-inflamed, immune-excluded, and immune-desert phenotypes, and their TME characteristics were highly consistent with different clinical outcomes and biological processes. Additionally, an m6A-related scoring system was developed to quantify the m6A modification pattern of individual samples. Low scores indicated high survival rates and high levels of immune activation, whereas high scores indicated stromal activation and tumor malignancy. Furthermore, the m6A-related scores were correlated with tumor mutation loads and various clinical traits, including molecular or histological subtypes and clinical stage or grade, and the score had predictive values across all digestive system tumors and even in all tumor types. Notably, a low score was linked to improved responses to anti-PD-1/L1 and anti-CTLA4 immunotherapy in three independent cohorts. This study has expanded the important role of m6A regulator-related genes in shaping TME diversity and clinical/biological traits of GC. The developed scoring system could help develop more effective immunotherapy strategies and personalized treatment guidance.
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Affiliation(s)
- Bin Peng
- Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, State Key Laboratory of Respiratory Disease, The Fifth Affiliated Hospital, Guangzhou Medical University, The Fifth Clinical College of Guangzhou Medical University, Guangzhou, China
| | - Yinglin Lin
- Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, State Key Laboratory of Respiratory Disease, The Fifth Affiliated Hospital, Guangzhou Medical University, The Fifth Clinical College of Guangzhou Medical University, Guangzhou, China
| | - Gao Yi
- Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, State Key Laboratory of Respiratory Disease, The Fifth Affiliated Hospital, Guangzhou Medical University, The Fifth Clinical College of Guangzhou Medical University, Guangzhou, China
| | - Mingzhen Lin
- Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, State Key Laboratory of Respiratory Disease, The Fifth Affiliated Hospital, Guangzhou Medical University, The Fifth Clinical College of Guangzhou Medical University, Guangzhou, China
| | - Yao Xiao
- Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, State Key Laboratory of Respiratory Disease, The Fifth Affiliated Hospital, Guangzhou Medical University, The Fifth Clinical College of Guangzhou Medical University, Guangzhou, China
| | - Yezhenghong Qiu
- Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, State Key Laboratory of Respiratory Disease, The Fifth Affiliated Hospital, Guangzhou Medical University, The Fifth Clinical College of Guangzhou Medical University, Guangzhou, China
| | - Wenxia Yao
- Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, State Key Laboratory of Respiratory Disease, The Fifth Affiliated Hospital, Guangzhou Medical University, The Fifth Clinical College of Guangzhou Medical University, Guangzhou, China.
| | - Xinke Zhou
- Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, State Key Laboratory of Respiratory Disease, The Fifth Affiliated Hospital, Guangzhou Medical University, The Fifth Clinical College of Guangzhou Medical University, Guangzhou, China.
| | - Zhaoyu Liu
- Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, State Key Laboratory of Respiratory Disease, The Fifth Affiliated Hospital, Guangzhou Medical University, The Fifth Clinical College of Guangzhou Medical University, Guangzhou, China.
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14
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Mohammed O, Gizaw ST, Degef M. Potential diagnostic, prognostic, and predictive biomarkers of gastric cancer. Health Sci Rep 2024; 7:e2261. [PMID: 39040881 PMCID: PMC11260885 DOI: 10.1002/hsr2.2261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 06/29/2024] [Accepted: 07/04/2024] [Indexed: 07/24/2024] Open
Abstract
Background Gastric cancer (GC), a malignant epithelial tumor, is the fourth leading cause of cancer-related death worldwide. Therapeutic strategies for GC, despite the biggest challenges, can significantly improve survival rates through early detection and effective screening methods. Aim To provide brief information on the necessity of multiple specific diagnostic, prognostic, and predictive markers for GC. Methods This review was conducted using a variety of search engines, including PubMed Central, Scopus, Web of Science, Google Scholar, and others. Results Some potential biomarkers that provide essential information include circulating tumor cells (CTCs), DNA methylation, claudin 18.2, fibroblast growth factor receptor 2 (FGFR2), long noncoding RNAs (lncRNAs), cell-free DNA (cfDNA), microRNAs, and serum pepsinogens. Conclusion Multiple tumor markers are essential for screening, tumor identification, staging, prognostic assessment, and monitoring recurrence after therapy due to the absence of a single tumor indicator for diagnosing, prognosticating, and predicting GC.
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Affiliation(s)
- Ousman Mohammed
- Department of Medical Laboratory SciencesCollege of Medicine and Health Sciences, Wollo UniversityDessieEthiopia
| | - Solomon Tebeje Gizaw
- Department of Medical BiochemistrySchool of Medicine, College of Health Sciences, AAUAddis AbabaEthiopia
| | - Maria Degef
- Department of Medical BiochemistrySchool of Medicine, College of Health Sciences, AAUAddis AbabaEthiopia
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15
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Jahantab MB, Salehi M, Koushki M, Farrokhi Yekta R, Amiri-Dashatan N, Rezaei-Tavirani M. Modelling of miRNA-mRNA Network to Identify Gene Signatures with Diagnostic and Prognostic Value in Gastric Cancer: Evidence from In-Silico and In-Vitro Studies. Rep Biochem Mol Biol 2024; 13:281-300. [PMID: 39995653 PMCID: PMC11847593 DOI: 10.61186/rbmb.13.2.281] [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: 07/09/2024] [Accepted: 12/08/2024] [Indexed: 02/26/2025]
Abstract
Background Gastric cancer (GC) is a prevalent malignancy with high recurrence. Advances in systems biology have identified molecular pathways and biomarkers. This study focuses on discovering gene and miRNA biomarkers for diagnosing and predicting survival in GC patients. Methods Three sets of genes (GSE19826, GSE81948, and GSE112369) and two sets of miRNA expression (GSE26595, GSE78775) were obtained from the Gene Expression Omnibus (GEO), and subsequently, differentially expressed genes (DEGs) and miRNAs (DEMs) were identified. Functional pathway enrichment, DEG-miR-TF-protein-protein interaction network, DEM-mRNA network, ROC curve, and survival analyses were performed. Finally, qRT-PCR was applied to validate our results. Results From the high-throughput profiling studies of GC, we investigated 10 candidate mRNA and 7 candidate miRNAs as potential biomarkers. Expression analysis of these hubs revealed that 5 miRNAs (including miR-141-3p, miR-204-5p, miR-338-3p, miR-609, and miR-369-5p) were significantly upregulated compared to the controls. The genes with the highest degree included 6 upregulated and 4 downregulated genes in tumor samples compared to controls. The expression of miR-141-3p, miR-204-5p, SESTD1, and ANTXR1 were verified in vitro from these hub DEMs and DEGs. The findings indicated a decrease in the expression of miR-141-3p and miR-204-5p and increased expression of SESTD1 and ANTXR1 in GC cell lines compared to the GES-1 cell line. Conclusions The current investigation successfully recognized a set of prospective miRNAs and genes that may serve as potential biomarkers for GC's early diagnosis and prognosis.
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Affiliation(s)
- Mohammad Bagher Jahantab
- Clinical Research Development Unit, Shahid Jalil Hospital, Yasuj University of Medical Sciences, Yasuj, Iran.
| | - Mohammad Salehi
- Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
| | - Mehdi Koushki
- Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.
- Department of Clinical Biochemistry, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
| | - Reyhaneh Farrokhi Yekta
- Proteomics Research Center, School of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Nasrin Amiri-Dashatan
- Proteomics Research Center, School of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Zanjan Metabolic Diseases Research Center, Health and Metabolic Diseases Research Institute, Zanjan University of Medical Sciences, Zanjan, Iran.
| | - Mostafa Rezaei-Tavirani
- Proteomics Research Center, School of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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16
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Yang K, Lu R, Mei J, Cao K, Zeng T, Hua Y, Huang X, Li W, Yin Y. The war between the immune system and the tumor - using immune biomarkers as tracers. Biomark Res 2024; 12:51. [PMID: 38816871 PMCID: PMC11137916 DOI: 10.1186/s40364-024-00599-5] [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: 12/06/2023] [Accepted: 05/10/2024] [Indexed: 06/01/2024] Open
Abstract
Nowadays, immunotherapy is one of the most promising anti-tumor therapeutic strategy. Specifically, immune-related targets can be used to predict the efficacy and side effects of immunotherapy and monitor the tumor immune response. In the past few decades, increasing numbers of novel immune biomarkers have been found to participate in certain links of the tumor immunity to contribute to the formation of immunosuppression and have entered clinical trials. Here, we systematically reviewed the oncogenesis and progression of cancer in the view of anti-tumor immunity, particularly in terms of tumor antigen expression (related to tumor immunogenicity) and tumor innate immunity to complement the cancer-immune cycle. From the perspective of integrated management of chronic cancer, we also appraised emerging factors affecting tumor immunity (including metabolic, microbial, and exercise-related markers). We finally summarized the clinical studies and applications based on immune biomarkers. Overall, immune biomarkers participate in promoting the development of more precise and individualized immunotherapy by predicting, monitoring, and regulating tumor immune response. Therefore, targeting immune biomarkers may lead to the development of innovative clinical applications.
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Affiliation(s)
- Kai Yang
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, P. R. China
| | - Rongrong Lu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, P. R. China
| | - Jie Mei
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, P. R. China
| | - Kai Cao
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, P. R. China
| | - Tianyu Zeng
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, P. R. China
| | - Yijia Hua
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, P. R. China
- Gusu School, Nanjing Medical University, Nanjing, China
| | - Xiang Huang
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, P. R. China.
| | - Wei Li
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, P. R. China.
| | - Yongmei Yin
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, P. R. China.
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Sun Z, Sun J, Hu H, Han S, Ma P, Zuo B, Wang Z, Liu Z. A novel microRNA miR-4433a-3p as a potential diagnostic biomarker for lung adenocarcinoma. Heliyon 2024; 10:e30646. [PMID: 38765119 PMCID: PMC11101798 DOI: 10.1016/j.heliyon.2024.e30646] [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: 06/28/2023] [Revised: 05/01/2024] [Accepted: 05/01/2024] [Indexed: 05/21/2024] Open
Abstract
Background Lung adenocarcinoma is one of the leading causes of cancer-related deaths because of the lack of early specific clinical indicators. MicroRNAs (miRNAs) have become the focus in lung cancer diagnosis. Further studies are required to explore miRNA expression in the serum of lung adenocarcinoma patients and their correlation with therapy and analyse specific messenger RNA targets to improve the specificity and sensitivity of early diagnosis. Methods The Toray 3D-Gene miRNA array was used to compare the expression levels of various miRNAs in the sera of patients with lung adenocarcinoma and healthy volunteers. Highly expressed miRNAs were selected for further analysis. To verify the screening results, serum and pleural fluid samples were analysed using qRT-PCR. Serum levels of the miRNAs and their correlation with the clinical information of patients with lung adenocarcinoma were analysed. The functions of miRNAs were further analysed using the Kyoto Encyclopedia of Gene and Genomes and Gene Ontology databases. Results Microarray analysis identified 60 and 50 miRNAs with upregulated and downregulated expressions, respectively, in the serum of patients with lung adenocarcinoma compared to those in healthy individuals. Using qRT-qPCR to detection of miRNAs expression in the serum or pleural effusion of patients with early and advanced lung adenocarcinoma, we found that miR-4433a-3p could be used as a diagnostic marker and therapeutic evaluation indicator for lung adenocarcinoma. Serum of miR-4433a-3p levels significantly correlated with the clinical stage. miR-4433a-3p may be more suitable than other tumour markers for the early diagnosis and evaluation of therapeutic effects in lung adenocarcinoma. miR-4433a-3p may affect tumour growth and metastasis by acting on target genes (PIK3CD, UBE2J2, ICMT, PRDM16 and others) and regulating tumour-related signalling pathways (MAPK signal pathway, Ras signalling pathway and others). Conclusion miR-4433a-3p may serve as a biomarker for the early diagnosis of lung adenocarcinoma and monitoring of therapeutic effects.
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Affiliation(s)
- Zhixiao Sun
- Department of Pulmonary and Critical Care Medicine, The Yancheng Clinical College of Xuzhou Medical University, The First People's Hospital of Yancheng, China
- Department of Central Laboratory, The Yancheng Clinical College of Xuzhou Medical University, The First People's Hospital of Yancheng, China
| | - Jian Sun
- Department of Cardiothoracic Surgery, The Yancheng Clinical College of Xuzhou Medical University, The First People's Hospital of Yancheng, China
| | - Hang Hu
- Department of Pulmonary and Critical Care Medicine, The Yancheng Clinical College of Xuzhou Medical University, The First People's Hospital of Yancheng, China
| | - Shuhua Han
- Department of Pulmonary and Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, China
| | - Panpan Ma
- Department of Clinical Laboratory, The Yancheng Clinical College of Xuzhou Medical University, The First People's Hospital of Yancheng, China
| | - Bingqing Zuo
- Department of Pulmonary and Critical Care Medicine, The Yancheng Clinical College of Xuzhou Medical University, The First People's Hospital of Yancheng, China
| | - Zheng Wang
- Department of Chronic Disease Medical Center, The Yancheng Clinical College of Xuzhou Medical University, The First People's Hospital of Yancheng, China
| | - Zhongxiang Liu
- Department of Pulmonary and Critical Care Medicine, The Yancheng Clinical College of Xuzhou Medical University, The First People's Hospital of Yancheng, China
- Department of Central Laboratory, The Yancheng Clinical College of Xuzhou Medical University, The First People's Hospital of Yancheng, China
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Feng T, Jie M, Deng K, Yang J, Jiang H. Targeted plasma proteomic analysis uncovers a high-performance biomarker panel for early diagnosis of gastric cancer. Clin Chim Acta 2024; 558:119675. [PMID: 38631604 DOI: 10.1016/j.cca.2024.119675] [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: 12/28/2023] [Revised: 03/30/2024] [Accepted: 04/14/2024] [Indexed: 04/19/2024]
Abstract
BACKGROUND Gastric cancer (GC) is characterized by high morbidity, high mortality and low early diagnosis rate. Early diagnosis plays a crucial role in radically treating GC. The aim of this study was to identify plasma biomarkers for GC and early GC diagnosis. METHODS We quantified 369 protein levels with plasma samples from discovery cohort (n = 88) and validation cohort (n = 50) via high-throughput proximity extension assay (PEA) utilizing the Olink-Explore-384-Cardiometabolic panel. The multi-protein signatures were derived from LASSO and Ridge regression models. RESULTS In the discovery cohort, 13 proteins (GDF15, ITIH3, BOC, DPP7, EGFR, AMY2A, CCDC80, CD163, GPNMB, LTBP2, CTSZ, CCL18 and NECTIN2) were identified to distinguish GC (Stage I-IV) and early GC (HGIN-I) groups from control group with AUC of 0.994 and AUC of 0.998, severally. The validation cohort yielded AUC of 0.930 and AUC of 0.818 for GC and early GC, respectively. CONCLUSIONS This study identified a multi-protein signature with the potential to benefit clinical GC diagnosis, especially for Asian and early GC patients, which may contribute to the development of a less-invasive, convenient, and efficient early screening tool, promoting early diagnosis and treatment of GC and ultimately improving patient survival.
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Affiliation(s)
- Tong Feng
- State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
| | - Minwen Jie
- Laboratory for Aging and Cancer Research, Frontiers Science Center Disease-related Molecular Network, State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
| | - Kai Deng
- Department of Gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
| | - Jinlin Yang
- Department of Gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
| | - Hao Jiang
- Laboratory for Aging and Cancer Research, Frontiers Science Center Disease-related Molecular Network, State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
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19
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Wang X, Wang C, Han W, Ma C, Sun J, Wang T, Hui Z, Lei S, Wang R. Bibliometric and visualized analysis of global research on microRNAs in gastric cancer: from 2013 to 2023. Front Oncol 2024; 14:1374743. [PMID: 38800413 PMCID: PMC11116657 DOI: 10.3389/fonc.2024.1374743] [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: 01/22/2024] [Accepted: 04/29/2024] [Indexed: 05/29/2024] Open
Abstract
Gastric cancer (GC) imposes a heavy burden on global public health, and microRNAs (miRNAs) play a crucial role in the diagnosis and treatment of GC. Therefore, it is necessary to clarify the hotspots and frontiers in the field of miRNAs in GC to guide future research. A total of 2,051 publications related to miRNAs in GC from January 2013 to December 2023 were searched from the Web of Science Core Collection database. CiteSpace was used to identify research hotspots and delineate developmental trends. In the past decade, China, Nanjing Medical University, and Ba Yi were the most contributing research country, institute, and author in this field, respectively. The role of miRNAs as biomarkers in GC, the mechanism of miRNAs in the progression of GC, and the impact of the mutual effects between miRNAs and Helicobacter pylori on GC have been regarded as the research hotspots. The mechanisms of miRNAs on glucose metabolism and the application of the roles of circular RNAs as miRNA sponges in GC treatment will likely be frontiers. Overall, this study called for strengthened cooperation to identify targets and therapeutic regimes for local specificity and high-risk GC types, and to promote the translation of research results into clinical practice.
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Affiliation(s)
- Xiaoqin Wang
- Department of Pediatrics, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- School of Nursing, Xi’an Jiaotong University Health Science Center, Xi’an, China
| | - Caihua Wang
- School of Nursing, Xi’an Jiaotong University Health Science Center, Xi’an, China
| | - Wenjin Han
- School of Nursing, Xi’an Jiaotong University Health Science Center, Xi’an, China
| | - Congmin Ma
- School of Nursing, Xi’an Jiaotong University Health Science Center, Xi’an, China
| | - Jiaru Sun
- School of Nursing, Xi’an Vocational and Technical College, Xi’an, China
| | - Tianmeng Wang
- School of Nursing, Xi’an Jiaotong University Health Science Center, Xi’an, China
| | - Zhaozhao Hui
- School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, China
| | - Shuangyan Lei
- Department of Radiotherapy, Shaanxi Cancer Hospital, Xi’an, China
| | - Ronghua Wang
- Department of Pediatrics, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
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20
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Zhang K, Zhao J, Bi Z, Feng Y, Zhang H, Zhang J, Qin X, Zhao Y, Niu R, Mei X, He Z, Yang J, Lv J, Guo W. Mechanism of miR-98-5p in gastric cancer cell proliferation, migration, and invasion through the USP44/CTCFL axis. Toxicol Res (Camb) 2024; 13:tfae040. [PMID: 38500512 PMCID: PMC10944557 DOI: 10.1093/toxres/tfae040] [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: 11/15/2023] [Revised: 01/28/2024] [Accepted: 02/02/2024] [Indexed: 03/20/2024] Open
Abstract
Objectives Gastric cancer (GC) is the leading digestive malignancy with high incidence and mortality rate. microRNAs (miRs) play an important role in GC progresssion. This study aimed to investigate the effect of miR-98-5p on proliferation, migration, and invasion of GC cells. Methods The expression levels of miR-98-5p, ubiquitin specific peptidase 44 (USP44), and CCCTCbinding factor-like (CTCFL) in GC tissues and cells were identified using reversetranscription quantitative polymerase chain reaction and Western blot assay. The relationship between miR-98-5p expression/USP44 and the clinicopathological features in GC patients was analyzed. GC cell proliferation, invasion, and migration were evaluated by cell counting kit-8 and clone formation assays and Transwell assays. The bindings of miR-98-5p to USP44 and USP44 to CTCFL were examined using dualluciferase assay and co-immunoprecipitation. GC cells were treated with MG132 and the ubiquitination level of CTCFL was examined using ubiquitination assay. Rescue experiments were performed to verify the roles of USP44 and CTCFL in GC cells. Results miR-98-5p was downregulated in GC. miR-98-5p overexpression inhibited the proliferation, migration, and invasion of GC cells. miR-98-5p inhibited USP44 expression. USP44 bound to CTCFL and limited ubiquitination degradation of CTCFL. Overexpression of USP44 and CTCFL attenuated the inhibitory effects of miR-98-5p overexpression on GC cell progression. Conclusion miR-98-5p overexpression limited USP44-mediated CTCFL deubiquitination, and suppressed CTCFL expression, mitigating GC cell proliferation, migration, and invasion.
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Affiliation(s)
- Kangkang Zhang
- Department of gastrointestinal surgery, Changzhi Medical College Affiliated Heji Hospital, No. 271 Taihang East Street, Luzhou District, Changzhi, Shanxi 046000, China
| | - Jinjiang Zhao
- Department of gastrointestinal surgery, Changzhi Medical College Affiliated Heji Hospital, No. 271 Taihang East Street, Luzhou District, Changzhi, Shanxi 046000, China
| | - Zhibin Bi
- Department of gastrointestinal surgery, Changzhi Medical College Affiliated Heji Hospital, No. 271 Taihang East Street, Luzhou District, Changzhi, Shanxi 046000, China
| | - Yafei Feng
- Department of gastrointestinal surgery, Changzhi Medical College Affiliated Heji Hospital, No. 271 Taihang East Street, Luzhou District, Changzhi, Shanxi 046000, China
| | - Huipeng Zhang
- Department of gastrointestinal surgery, Changzhi Medical College Affiliated Heji Hospital, No. 271 Taihang East Street, Luzhou District, Changzhi, Shanxi 046000, China
| | - Jinjie Zhang
- Department of gastrointestinal surgery, Changzhi Medical College Affiliated Heji Hospital, No. 271 Taihang East Street, Luzhou District, Changzhi, Shanxi 046000, China
| | - Xiaowei Qin
- Department of gastrointestinal surgery, Changzhi Medical College Affiliated Heji Hospital, No. 271 Taihang East Street, Luzhou District, Changzhi, Shanxi 046000, China
| | - Yanbo Zhao
- Department of gastrointestinal surgery, Changzhi Medical College Affiliated Heji Hospital, No. 271 Taihang East Street, Luzhou District, Changzhi, Shanxi 046000, China
| | - Ruilong Niu
- Department of gastrointestinal surgery, Changzhi Medical College Affiliated Heji Hospital, No. 271 Taihang East Street, Luzhou District, Changzhi, Shanxi 046000, China
| | - Xianghuang Mei
- Department of gastrointestinal surgery, Changzhi Medical College Affiliated Heji Hospital, No. 271 Taihang East Street, Luzhou District, Changzhi, Shanxi 046000, China
| | - Zhipeng He
- Department of gastrointestinal surgery, Changzhi Medical College Affiliated Heji Hospital, No. 271 Taihang East Street, Luzhou District, Changzhi, Shanxi 046000, China
| | - Jingcheng Yang
- Department of gastrointestinal surgery, Changzhi Medical College Affiliated Heji Hospital, No. 271 Taihang East Street, Luzhou District, Changzhi, Shanxi 046000, China
| | - Jiake Lv
- Department of gastrointestinal surgery, Changzhi Medical College Affiliated Heji Hospital, No. 271 Taihang East Street, Luzhou District, Changzhi, Shanxi 046000, China
| | - Wei Guo
- Department of gastrointestinal surgery, Changzhi Medical College Affiliated Heji Hospital, No. 271 Taihang East Street, Luzhou District, Changzhi, Shanxi 046000, China
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21
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Hakami ZH. Biomarker discovery and validation for gastrointestinal tumors: A comprehensive review of colorectal, gastric, and liver cancers. Pathol Res Pract 2024; 255:155216. [PMID: 38401376 DOI: 10.1016/j.prp.2024.155216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2023] [Revised: 02/07/2024] [Accepted: 02/15/2024] [Indexed: 02/26/2024]
Abstract
Gastrointestinal (GI) malignancies, encompassing gastric, hepatic, colonic, and rectal cancers, are prevalent forms of cancer globally and contribute substantially to cancer-related mortality. Although there have been improvements in methods for diagnosing and treating GI cancers, the chances of survival for these types of cancers are still extremely low. According to the World Cancer Research International Fund's most recent figures, stomach cancer was responsible for roughly one million deaths worldwide in 2020. This emphasizes the importance of developing more effective tools for detecting, diagnosing, and predicting the outcome of these cancers at an early stage. Biomarkers, quantitative indications of biological processes or disease states, have emerged as promising techniques for enhancing the diagnosis and prognosis of GI malignancies. Recently, there has been a considerable endeavor to discover and authenticate biomarkers for various GI cancers by the utilization of diverse methodologies, including genomics, proteomics, and metabolomics. This review provides a thorough examination of the current state of biomarker research in the field of gastrointestinal malignancies, with a specific emphasis on colorectal, stomach, and liver cancers. A thorough literature search was performed on prominent databases such as PubMed, Scopus, and Web of Science to find pertinent papers published until November, 2023 for the purpose of compiling this review. The diverse categories of biomarkers, encompassing genetic, epigenetic, and protein-based biomarkers, and their potential utility in the fields of diagnosis, prognosis, and treatment selection, are explored. Recent progress in identifying and confirming biomarkers, as well as the obstacles that persist in employing biomarkers in clinical settings are emphasized. The utilization of biomarkers in GI cancers has significant potential in enhancing patient outcomes. Ongoing research is expected to uncover more efficient biomarkers for the diagnosis and prognosis of these cancers.
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Affiliation(s)
- Zaki H Hakami
- Department of Medical Laboratory Technology, Faculty of Applied Medical Science, Jazan University, Jazan 45142, Saudi Arabia.
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22
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Xue J, Qin S, Ren N, Guo B, Shi X, Jia E. Extracellular vesicle biomarkers in circulation for the diagnosis of gastric cancer: A systematic review and meta‑analysis. Oncol Lett 2023; 26:423. [PMID: 37664665 PMCID: PMC10472029 DOI: 10.3892/ol.2023.14009] [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: 11/28/2022] [Accepted: 06/14/2023] [Indexed: 09/05/2023] Open
Abstract
The prognosis of a gastric cancer (GC) diagnosis is poor due to the current lack of effective early diagnostic methods. Extracellular vesicle (EV) biomarkers have previously demonstrated strong diagnostic efficiency for certain types of cancer, including pancreatic and lung cancer. The present review aimed to summarize the diagnostic value of circulating EV biomarkers for early stage GC. The PubMed, Medline and Web of Science databases were searched from May 1983 to September 18, 2022. All studies that reported the diagnostic performance of EV biomarkers for GC were included for analysis. Overall, 27 studies were selected containing 2,831 patients with GC and 2,117 controls. A total of 58 EV RNAs were reported in 26 studies, including 39 microRNAs (miRNAs), 10 long non-coding RNAs (lncRNAs), five circular RNAs, three PIWI-interacting RNAs and one mRNA, in addition to one protein in the remaining study. Meta-analysis of the aforementioned studies demonstrated that the pooled sensitivity, specificity and AUC value of the total RNAs were 84, 67% and 0.822, respectively. The diagnostic values of miRNAs were consistent with the total RNA, as the pooled sensitivity, specificity and AUC value were 84, 67% and 0.808, respectively. The pooled sensitivity, specificity and AUC values of lncRNAs were 89, 69% and 0.872, respectively, markedly higher compared with that of miRNAs. A total of five studies reported the diagnostic performance of EV RNA panels for early stage GC and reported powerful diagnostic values with a pooled sensitivity, specificity and AUC value of 80, 77% and 0.879, respectively. Circulating EV RNAs could have the potential to be used in the future as effective, noninvasive biomarkers for early GC diagnosis. Further research in this field is necessary to translate these findings into clinical practice.
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Affiliation(s)
- Jinru Xue
- Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Jilin, Changchun 130000, P.R. China
| | - Shaoyou Qin
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, Jilin, Changchun 130000, P.R. China
| | - Na Ren
- Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Jilin, Changchun 130000, P.R. China
| | - Bo Guo
- Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Jilin, Changchun 130000, P.R. China
| | - Xianquan Shi
- Department of Ultrasound, Beijing Friendship Hospital of Capital Medical University, Beijing 100050, P.R. China
| | - Erna Jia
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, Jilin, Changchun 130000, P.R. China
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23
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Jiang C, Zhang J, Wang W, Shan Z, Sun F, Tan Y, Tong Y, Qiu Y. Extracellular vesicles in gastric cancer: role of exosomal lncRNA and microRNA as diagnostic and therapeutic targets. Front Physiol 2023; 14:1158839. [PMID: 37664422 PMCID: PMC10469264 DOI: 10.3389/fphys.2023.1158839] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Accepted: 07/31/2023] [Indexed: 09/05/2023] Open
Abstract
Extracellular vesicles (EVs), including exosomes, play a crucial role in intercellular communication and have emerged as important mediators in the development and progression of gastric cancer. This review discusses the current understanding of the role of EVs, particularly exosomal lncRNA and microRNA, in gastric cancer and their potential as diagnostic and therapeutic targets. Exosomes are small membrane-bound particles secreted by both cancer cells and stromal cells within the tumor microenvironment. They contain various ncRNA and biomolecules, which can be transferred to recipient cells to promote tumor growth and metastasis. In this review, we highlighted the importance of exosomal lncRNA and microRNA in gastric cancer. Exosomal lncRNAs have been shown to regulate gene expression by interacting with transcription factors or chromatin-modifying enzymes, which regulate gene expression by binding to target mRNAs. We also discuss the potential use of exosomal lncRNAs and microRNAs as diagnostic biomarkers for gastric cancer. Exosomes can be isolated from various bodily fluids, including blood, urine, and saliva. They contain specific molecules that reflect the molecular characteristics of the tumor, making them promising candidates for non-invasive diagnostic tests. Finally, the potential of targeting exosomal lncRNAs and microRNAs as a therapeutic strategy for gastric cancer were reviewed as wee. Inhibition of specific molecules within exosomes has been shown to suppress tumor growth and metastasis in preclinical models. In conclusion, this review article provides an overview of the current understanding of the role of exosomal lncRNA and microRNA in gastric cancer. We suggest that further research into these molecules could lead to new diagnostic tools and therapeutic strategies for this deadly disease.
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Affiliation(s)
- Chengyao Jiang
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Jianjun Zhang
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Wentao Wang
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Zexing Shan
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Fan Sun
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Yuen Tan
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Yilin Tong
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Yue Qiu
- Medical Oncology Department of Gastrointestinal Cancer, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, China
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24
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Tang B, Li M, Xu Y, Li X. N 6-methyladenosine (m 6A) writer KIAA1429 accelerates gastric cancer oxaliplatin chemoresistance by targeting FOXM1. J Cancer Res Clin Oncol 2023; 149:5037-5045. [PMID: 36326914 DOI: 10.1007/s00432-022-04426-y] [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: 09/21/2022] [Accepted: 10/16/2022] [Indexed: 11/06/2022]
Abstract
PURPOSE Chemical modification plays a critical role in regulating human cancer progression, especially N6-methyladenosine (m6A). However, m6A writer KIAA1429-mediated m6A modification in gastric cancer (GC) tumorigenesis remains largely unknown. METHODS The levels of mRNA and protein were detected using RT-qPCR and western blot. The half maximal inhibitory concentration (IC50) of oxaliplatin (OXA) resistance is detected using CCK-8 assay. The binding within moleculars was identified using RIP-PCR. RESULTS Results found that KIAA1429 was upregulated in GC tissue samples and its high expression acted as a prognostic factor of poor survival in patients with GC. Functional assays indicated that KIAA1429 promoted the proliferation of GC cells, besides, KIAA1429 accelerated the half maximal inhibitory concentration (IC50) of oxaliplatin (OXA) resistance. Mechanistically, online prediction found that there was possible m6A modification site on FOXM1 mRNA. KIAA1429 could target the m6A modification site on FOXM1. Notably, KIAA1429 facilitated the GC OXA resistance in GC cells by promoting FOXM1 mRNA stability. CONCLUSIONS Taken together, our study reveals the functions and mechanism for KIAA1429 and exposes KIAA1429 as a key player in GC chemoresistance.
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Affiliation(s)
- Bingxi Tang
- Department of Gastroenterology, Zibo Central Hospital, Zibo, 255036, China
| | - Mingdong Li
- Department of Gastroenterology, Zibo Central Hospital, Zibo, 255036, China
| | - Yanbing Xu
- Department of General Surgery, Zibo Central Hospital, Zibo, 255036, China
| | - Xinli Li
- Department of Clinical Laboratory, Zibo Central Hospital, Zibo, 255036, China.
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Gareev I, Ahmad A, Wang J, Beilerli A, Ilyasova T, Sufianov A, Beylerli O. Gastric juice non-coding RNAs as potential biomarkers for gastric cancer. Front Physiol 2023; 14:1179582. [PMID: 37179825 PMCID: PMC10169709 DOI: 10.3389/fphys.2023.1179582] [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: 03/04/2023] [Accepted: 04/18/2023] [Indexed: 05/15/2023] Open
Abstract
Gastric cancer (GC), being one of the most common malignant human tumors, occupies the second position in the structure of mortality in men and women. High rates of morbidity and mortality in this pathology determine its extremely high clinical and social significance. Diagnosis and timely treatment of precancerous pathology is the main way to reduce morbidity and mortality, and early detection of GC and its adequate treatment improve prognosis. The ability to accurately predict the development of GC and start treatment on time, as well as the ability to determine the stage of the disease if the diagnosis is confirmed - non-invasive biomarkers can become the key to solving these and many other problems of modern medicine. One of the promising biomarkers being studied are non-coding RNAs, namely, miсroRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). They are involved in a wide range of processes, including apoptosis, proliferation, differentiation, angiogenesis, which play a critical role in the development of GC oncogenesis. In addition, they are quite specific and stable due to their carriers (extracellular vesicles or Argonaute 2 protein) and can be detected in various human biological fluids, in particular gastric juice. Thus, miRNAs, lncRNAs, and circRNAs isolated from the gastric juice of GC patients are promising preventive, diagnostic and prognostic non-invasive biomarkers. This review article presents the characteristics of circulating or extracellular miRNAs, lncRNAs, and circRNAs in gastric juice, allowing their use in the GC preventive, diagnosis, prognosis and monitoring therapy.
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Affiliation(s)
- Ilgiz Gareev
- Educational and Scientific Institute of Neurosurgery, Peoples’ Friendship University of Russia (RUDN University), Moscow, Russian
| | - Aamir Ahmad
- Academic Health System, Hamad Medical Corporation, Interim Translational Research Institute, Doha, Qatar
| | - Jiaqi Wang
- Department of Urology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Aferin Beilerli
- Department of Obstetrics and Gynecology, Tyumen State Medical University, Tyumen, Russia
| | - Tatiana Ilyasova
- Department of Internal Diseases, Bashkir State Medical University, Ufa, Russia
| | - Albert Sufianov
- Educational and Scientific Institute of Neurosurgery, Peoples’ Friendship University of Russia (RUDN University), Moscow, Russian
- Department of Neurosurgery, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Ozal Beylerli
- Educational and Scientific Institute of Neurosurgery, Peoples’ Friendship University of Russia (RUDN University), Moscow, Russian
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26
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Lopes C, Almeida TC, Pimentel-Nunes P, Dinis-Ribeiro M, Pereira C. Linking dysbiosis to precancerous stomach through inflammation: Deeper than and beyond imaging. Front Immunol 2023; 14:1134785. [PMID: 37063848 PMCID: PMC10102473 DOI: 10.3389/fimmu.2023.1134785] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Accepted: 03/17/2023] [Indexed: 04/03/2023] Open
Abstract
Upper gastrointestinal endoscopy is considered the gold standard for gastric lesions detection and surveillance, but it is still associated with a non-negligible rate of missing conditions. In the Era of Personalized Medicine, biomarkers could be the key to overcome missed lesions or to better predict recurrence, pushing the frontier of endoscopy to functional endoscopy. In the last decade, microbiota in gastric cancer has been extensively explored, with gastric carcinogenesis being associated with progressive dysbiosis. Helicobacter pylori infection has been considered the main causative agent of gastritis due to its interference in disrupting the acidic environment of the stomach through inflammatory mediators. Thus, does inflammation bridge the gap between gastric dysbiosis and the gastric carcinogenesis cascade and could the microbiota-inflammation axis-derived biomarkers be the answer to the unmet challenge of functional upper endoscopy? To address this question, in this review, the available evidence on the role of gastric dysbiosis and chronic inflammation in precancerous conditions of the stomach is summarized, particularly targeting the nuclear factor-κB (NF-κB), toll-like receptors (TLRs) and cyclooxygenase-2 (COX-2) pathways. Additionally, the potential of liquid biopsies as a non-invasive source and the clinical utility of studied biomarkers is also explored. Overall, and although most studies offer a mechanistic perspective linking a strong proinflammatory Th1 cell response associated with, but not limited to, chronic infection with Helicobacter pylori, promising data recently published highlights not only the diagnostic value of microbial biomarkers but also the potential of gastric juice as a liquid biopsy pushing forward the concept of functional endoscopy and personalized care in gastric cancer early diagnosis and surveillance.
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Affiliation(s)
- Catarina Lopes
- Precancerous Lesions and Early Cancer Management Group, Research Center of IPO Porto (CI‐IPOP)/Rise@CI‐IPOP (Health Research Group), Portuguese Institute of Oncology of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), Porto, Portugal
- CINTESIS – Center for Health Technology and Services Research, University of Porto, Porto, Portugal
- ICBAS-UP – Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, Portugal
| | - Tatiana C. Almeida
- Precancerous Lesions and Early Cancer Management Group, Research Center of IPO Porto (CI‐IPOP)/Rise@CI‐IPOP (Health Research Group), Portuguese Institute of Oncology of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), Porto, Portugal
| | - Pedro Pimentel-Nunes
- Department of Surgery and Physiology, Faculty of Medicine, University of Porto (FMUP), Porto, Portugal
- Department of Gastroenterology, Unilabs, Porto, Portugal
| | - Mário Dinis-Ribeiro
- Precancerous Lesions and Early Cancer Management Group, Research Center of IPO Porto (CI‐IPOP)/Rise@CI‐IPOP (Health Research Group), Portuguese Institute of Oncology of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), Porto, Portugal
- Department of Gastroenterology, Portuguese Institute of Oncology of Porto, Porto, Portugal
| | - Carina Pereira
- Precancerous Lesions and Early Cancer Management Group, Research Center of IPO Porto (CI‐IPOP)/Rise@CI‐IPOP (Health Research Group), Portuguese Institute of Oncology of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), Porto, Portugal
- CINTESIS – Center for Health Technology and Services Research, University of Porto, Porto, Portugal
- *Correspondence: Carina Pereira,
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Cancer Is Associated with the Emergence of Placenta-Reactive Autoantibodies. Biomedicines 2023; 11:biomedicines11020316. [PMID: 36830854 PMCID: PMC9953527 DOI: 10.3390/biomedicines11020316] [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: 12/15/2022] [Revised: 01/17/2023] [Accepted: 01/19/2023] [Indexed: 01/25/2023] Open
Abstract
Placenta-specific antigens are minimally expressed or unexpressed in normal adult tissues, while they are widely expressed in cancer. In the course of carcinogenesis, a vast array of autoantibodies (AAbs) is produced. Here, we used a quantitative approach to determine the reactivity of AAbs in the sera of patients with breast (BrC: N = 100, 100% female, median age: 51 years), gastric (GC: N = 30, 46.6% female, median age: 57 years), bladder (BC: N = 29, 34.4% female, median age: 57 years), and colorectal (CRC: N = 34, 41.1% female, median age: 51 years) cancers against first-trimester (FTP) and full-term placental proteome (TP) in comparison with age- and sex-matched non-cancer individuals. Human-on-human immunohistochemistry was used to determine reactive target cells in FTP. The effect of pregnancy on the emergence of placenta-reactive autoantibodies was tested using sera from pregnant women at different trimesters of pregnancy. Except for BC, patients with BrC (p < 0.0284), GC (p < 0.0002), and CRC (p < 0.0007) had significantly higher levels of placenta-reactive AAbs. BrC (p < 0.0001) and BC (p < 0.0409) in the early stages triggered higher autoantibody reactivity against FTP. The reactivities of BrC sera with FTP did not show an association with ER, PR, or HER2 expression. Pregnancy in the third trimester was associated with the induction of TP- and not FTP-reactive autoantibodies (=0.018). The reactivity of BrC sera with placental proteins was found to be independent of gravidity or abortion. BrC sera showed a very strong and specific pattern of reactivity with scattered cells beneath the syncytiotrophoblast layer. Our results reinforce the concept of the coevolution of placentation and cancer and shed light on the future clinical application of the placental proteome for the non-invasive early detection and treatment of cancer.
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Ma S, Zhou M, Xu Y, Gu X, Zou M, Abudushalamu G, Yao Y, Fan X, Wu G. Clinical application and detection techniques of liquid biopsy in gastric cancer. Mol Cancer 2023; 22:7. [PMID: 36627698 PMCID: PMC9832643 DOI: 10.1186/s12943-023-01715-z] [Citation(s) in RCA: 67] [Impact Index Per Article: 33.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 01/02/2023] [Indexed: 01/12/2023] Open
Abstract
Gastric cancer (GC) is one of the most common tumors worldwide and the leading cause of tumor-related mortality. Endoscopy and serological tumor marker testing are currently the main methods of GC screening, and treatment relies on surgical resection or chemotherapy. However, traditional examination and treatment methods are more harmful to patients and less sensitive and accurate. A minimally invasive method to respond to GC early screening, prognosis monitoring, treatment efficacy, and drug resistance situations is urgently needed. As a result, liquid biopsy techniques have received much attention in the clinical application of GC. The non-invasive liquid biopsy technique requires fewer samples, is reproducible, and can guide individualized patient treatment by monitoring patients' molecular-level changes in real-time. In this review, we introduced the clinical applications of circulating tumor cells, circulating free DNA, circulating tumor DNA, non-coding RNAs, exosomes, and proteins, which are the primary markers in liquid biopsy technology in GC. We also discuss the current limitations and future trends of liquid biopsy technology as applied to early clinical biopsy technology.
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Affiliation(s)
- Shuo Ma
- grid.452290.80000 0004 1760 6316Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, Nanjing, 210009 Jiangsu China ,grid.263826.b0000 0004 1761 0489Department of Laboratory Medicine, Medical School of Southeast University, Nanjing, 210009 Jiangsu China
| | - Meiling Zhou
- grid.452290.80000 0004 1760 6316Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, Nanjing, 210009 Jiangsu China ,grid.263826.b0000 0004 1761 0489Department of Laboratory Medicine, Medical School of Southeast University, Nanjing, 210009 Jiangsu China
| | - Yanhua Xu
- grid.452743.30000 0004 1788 4869Department of Laboratory Medicine, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, 225000 Jiangsu China
| | - Xinliang Gu
- grid.440642.00000 0004 0644 5481Department of Laboratory Medicine, Medical School, Affiliated Hospital of Nantong University, Nantong University, Nantong, 226001 Jiangsu China
| | - Mingyuan Zou
- grid.452290.80000 0004 1760 6316Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, Nanjing, 210009 Jiangsu China ,grid.263826.b0000 0004 1761 0489Department of Laboratory Medicine, Medical School of Southeast University, Nanjing, 210009 Jiangsu China
| | - Gulinaizhaer Abudushalamu
- grid.452290.80000 0004 1760 6316Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, Nanjing, 210009 Jiangsu China ,grid.263826.b0000 0004 1761 0489Department of Laboratory Medicine, Medical School of Southeast University, Nanjing, 210009 Jiangsu China
| | - Yuming Yao
- grid.452290.80000 0004 1760 6316Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, Nanjing, 210009 Jiangsu China ,grid.263826.b0000 0004 1761 0489Department of Laboratory Medicine, Medical School of Southeast University, Nanjing, 210009 Jiangsu China
| | - Xiaobo Fan
- grid.452290.80000 0004 1760 6316Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, Nanjing, 210009 Jiangsu China ,grid.263826.b0000 0004 1761 0489Department of Laboratory Medicine, Medical School of Southeast University, Nanjing, 210009 Jiangsu China
| | - Guoqiu Wu
- grid.452290.80000 0004 1760 6316Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, Nanjing, 210009 Jiangsu China ,grid.263826.b0000 0004 1761 0489Department of Laboratory Medicine, Medical School of Southeast University, Nanjing, 210009 Jiangsu China ,grid.263826.b0000 0004 1761 0489Jiangsu Provincial Key Laboratory of Critical Care Medicine, Southeast University, Nanjing, 210009 Jiangsu China
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Guo SS, Wang ZG. Salvianolic acid B from Salvia miltiorrhiza bunge: A potential antitumor agent. Front Pharmacol 2022; 13:1042745. [PMID: 36386172 PMCID: PMC9640750 DOI: 10.3389/fphar.2022.1042745] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 10/14/2022] [Indexed: 11/25/2022] Open
Abstract
Salvia miltiorrhiza Bunge (Lamiaceae) is a perennial herb widely found in China since ancient times with a high economic and medicinal value. Salvianolic acid B (Sal-B) is an important natural product derived from Salvia miltiorrhiza and this review summarizes the anticancer activity of Sal-B. Sal-B inhibits tumor growth and metastasis by targeting multiple cell signaling pathways. This review aims to review experimental studies to describe the possible anticancer mechanisms of Sal-B and confirm its potential as a therapeutic drug.
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Affiliation(s)
- Sha-Sha Guo
- Key Laboratory of Theory of TCM, Ministry of Education of China, Shandong University of Traditional Chinese Medicine, Jinan, China
- Institute of Traditional Chinese Medicine Literature and Culture, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Zhen-Guo Wang
- Key Laboratory of Theory of TCM, Ministry of Education of China, Shandong University of Traditional Chinese Medicine, Jinan, China
- Institute of Traditional Chinese Medicine Literature and Culture, Shandong University of Traditional Chinese Medicine, Jinan, China
- *Correspondence: Zhen-Guo Wang,
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