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Jin K, Mao Z, Tang Y, Feng W, Ju S, Jing R, Chen J, Zong W. tRF-23-R9J89O9N9:A novel liquid biopsy marker for diagnosis of hepatocellular carcinoma. Clin Chim Acta 2025; 572:120261. [PMID: 40147805 DOI: 10.1016/j.cca.2025.120261] [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: 01/20/2025] [Revised: 03/10/2025] [Accepted: 03/19/2025] [Indexed: 03/29/2025]
Abstract
BACKGROUND Non-coding small RNA, specifically tRNA-derived small RNAs (tsRNAs), are readily detectable in cancer patients, exhibit remarkable stability, and are present in high abundance. They play a significant role in tumor development. However, the clinical significance of serum tsRNAs in hepatocellular carcinoma (HCC) remains poorly understood. In this study, we explored the impact of a novel tsRNA, named tRF-23-R9J89O9N9, in the adjuvant diagnosis, disease monitoring, and prognosis assessment of HCC. METHODS The tRF-23-R9J89O9N9 was identified as the target molecule through screening the The Cancer Genome Atlas(TCGA) database. Its expression levels were measured using qRT-PCR. Various methods, including agarose gel electrophoresis, Sanger sequencing, gradient dilution experiments, room temperature stability tests, and repeated freeze-thaw assessments, were employed to evaluate the performance of tRF-23-R9J89O9N9. The correlation between tRF-23-R9J89O9N9 levels and clinicopathological parameters was analyzed using the χ2 test. The diagnostic value of tRF-23-R9J89O9N9 in HCC was assessed with ROC curve analysis, while the prognostic value was evaluated using Kaplan-Meier curves. RESULTS Serum tRF-23-R9J89O9N9 expression levels were significantly elevated in HCC patients, while levels in postoperative patients were restored to those of healthy subjects. Additionally, the expression of tRF-23-R9J89O9N9 related to TNM stage(P = 0.009), lymph node metastasis(P<0.0001), and degree of differentiation(P<0.0001). Furthermore, the combination of AFP, PIVKA-II, and CEA greatly improved the diagnostic value for HCC. Serum tRF-23-R9J89O9N9 was also identified as a potential biomarker for dynamic monitoring and prognosis of HCC. CONCLUSIONS tRF-23-R9J89O9N9 may regard as a potential novel biomarker for the adjuvant diagnosis of HCC.
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Affiliation(s)
- Kangfeng Jin
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China; Medical School of Nantong University, Nantong University, Nantong, Jiangsu, China; Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
| | - Zhiyun Mao
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China; Medical School of Nantong University, Nantong University, Nantong, Jiangsu, China; Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
| | - Yelan Tang
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China; Medical School of Nantong University, Nantong University, Nantong, Jiangsu, China; Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
| | - Wei Feng
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
| | - Shaoqing Ju
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
| | - Rongrong Jing
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
| | - Jianhui Chen
- Blood Transfusion Department of Yiwu Central Hospital, Yiwu, Zhejiang, China.
| | - Wei Zong
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
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Kong S, Xu YH, Zheng M, Ju SQ, Shi HC. Circ_0004592: An auxiliary diagnostic biomarker for gastric cancer. World J Gastrointest Oncol 2024; 16:2745-2756. [DOI: 10.4251/wjgo.v16.i6.2745] [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: 01/29/2024] [Revised: 03/12/2024] [Accepted: 04/12/2024] [Indexed: 06/13/2024] Open
Abstract
BACKGROUND Gastric cancer (GC) has a high mortality rate, and robust diagnostic biomarkers are currently lacking. However, the clinical relevance of circular RNAs (circRNAs) as GC biomarkers remains largely unexplored.
AIM To evaluate the potential of novel circRNA circ_0004592 in the early screening and prognosis of GC.
METHODS High-throughput sequencing of circRNAs was performed to screen for potential target molecules. Circ_0004592 expression was examined in GC tissues, cells, and plasma. Plasma samples were collected from healthy subjects’ patients, as well as from patients with benign lesions, precancerous lesions, and GC, whereafter the diagnostic accuracy of circ_0004592 was evaluated. The correlation between circ_0004592 levels in plasma and clinicopathological data of patients with GC was further analyzed.
RESULTS Circ_0004592 was upregulated in both the tissue and plasma of patients with GC. Further, circ_0004592 expression was higher in patients with precancerous lesions than in healthy controls while being highest in patients with GC. In the same patient, the postoperative plasma level of circ_0004592 was lower than that in the preoperative period. Moreover, circ_0004592 level was significantly correlated with tumor differentiation, tumor depth, and lymph node metastasis. The area under the curve (AUC) of plasma circ_0004592 exhibited high sensitivity and specificity for differentiating patients with GC from healthy donors. Diagnosis based on circ_0004592, carcinoembryonic antigen, and cancer antigen 199 achieved a superior AUC and was highly sensitive.
CONCLUSION Plasma circ_0004592 may represent a potential non-invasive auxiliary diagnostic biomarker for patients with GC.
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Affiliation(s)
- Shan Kong
- Department of Laboratory Medicine, Jiangsu Province Official Hospital, Nanjing 210000, Jiangsu Province, China
| | - Yan-Hua Xu
- Department of Laboratory Medicine, Northern Jiangsu People’s Hospital, Yangzhou 225000, Jiangsu Province, China
| | - Ming Zheng
- Department of Laboratory Medicine, The Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Shao-Qing Ju
- Department of Laboratory Medicine, The Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Heng-Chuan Shi
- Department of Laboratory Medicine, Jiangsu Province Official Hospital, Nanjing 210000, Jiangsu Province, China
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Kong S, Xu YH, Zheng M, Ju SQ, Shi HC. Circ_0004592: An auxiliary diagnostic biomarker for gastric cancer. World J Gastrointest Oncol 2024; 16:2757-2768. [PMID: 38994162 PMCID: PMC11236232 DOI: 10.4251/wjgo.v16.i6.2757] [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: 01/29/2024] [Revised: 03/12/2024] [Accepted: 04/12/2024] [Indexed: 06/13/2024] Open
Abstract
BACKGROUND Gastric cancer (GC) has a high mortality rate, and robust diagnostic biomarkers are currently lacking. However, the clinical relevance of circular RNAs (circRNAs) as GC biomarkers remains largely unexplored. AIM To evaluate the potential of novel circRNA circ_0004592 in the early screening and prognosis of GC. METHODS High-throughput sequencing of circRNAs was performed to screen for potential target molecules. Circ_0004592 expression was examined in GC tissues, cells, and plasma. Plasma samples were collected from healthy subjects' patients, as well as from patients with benign lesions, precancerous lesions, and GC, whereafter the diagnostic accuracy of circ_0004592 was evaluated. The correlation between circ_0004592 levels in plasma and clinicopathological data of patients with GC was further analyzed. RESULTS Circ_0004592 was upregulated in both the tissue and plasma of patients with GC. Further, circ_0004592 expression was higher in patients with precancerous lesions than in healthy controls while being highest in patients with GC. In the same patient, the postoperative plasma level of circ_0004592 was lower than that in the preoperative period. Moreover, circ_0004592 level was significantly correlated with tumor differentiation, tumor depth, and lymph node metastasis. The area under the curve (AUC) of plasma circ_0004592 exhibited high sensitivity and specificity for differentiating patients with GC from healthy donors. Diagnosis based on circ_0004592, carcinoembryonic antigen, and cancer antigen 199 achieved a superior AUC and was highly sensitive. CONCLUSION Plasma circ_0004592 may represent a potential non-invasive auxiliary diagnostic biomarker for patients with GC.
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Affiliation(s)
- Shan Kong
- Department of Laboratory Medicine, Jiangsu Province Official Hospital, Nanjing 210000, Jiangsu Province, China
| | - Yan-Hua Xu
- Department of Laboratory Medicine, Northern Jiangsu People’s Hospital, Yangzhou 225000, Jiangsu Province, China
| | - Ming Zheng
- Department of Laboratory Medicine, The Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Shao-Qing Ju
- Department of Laboratory Medicine, The Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Heng-Chuan Shi
- Department of Laboratory Medicine, Jiangsu Province Official Hospital, Nanjing 210000, Jiangsu Province, China
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Han HS, Lee KW. Liquid Biopsy: An Emerging Diagnostic, Prognostic, and Predictive Tool in Gastric Cancer. J Gastric Cancer 2024; 24:4-28. [PMID: 38225764 PMCID: PMC10774753 DOI: 10.5230/jgc.2024.24.e5] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 12/05/2023] [Accepted: 12/06/2023] [Indexed: 01/17/2024] Open
Abstract
Liquid biopsy, a minimally invasive procedure that causes minimal pain and complication risks to patients, has been extensively studied for cancer diagnosis and treatment. Moreover, it facilitates comprehensive quantification and serial assessment of the whole-body tumor burden. Several biosources obtained through liquid biopsy have been studied as important biomarkers for establishing early diagnosis, monitoring minimal residual disease, and predicting the prognosis and response to treatment in patients with cancer. Although the clinical application of liquid biopsy in gastric cancer is not as robust as that in other cancers, biomarker studies using liquid biopsy are being actively conducted in patients with gastric cancer. Herein, we aimed to review the role of various biosources that can be obtained from patients with gastric cancer through liquid biopsies, such as blood, saliva, gastric juice, urine, stool, peritoneal lavage fluid, and ascites, by dividing them into cellular and acellular components. In addition, we reviewed previous studies on the diagnostic, prognostic, and predictive biomarkers for gastric cancer using liquid biopsy and discussed the limitations of liquid biopsy and the challenges to overcome these limitations in patients with gastric cancer.
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Affiliation(s)
- Hye Sook Han
- Department of Internal Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Keun-Wook Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
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Zhang ZH, Bao YW, Zhao YJ, Wang JQ, Guo JT, Sun SY. Circulating tumor cells as potential prognostic biomarkers for early-stage pancreatic cancer: A systematic review and meta-analysis. World J Clin Oncol 2023; 14:504-517. [PMID: 38059182 PMCID: PMC10696218 DOI: 10.5306/wjco.v14.i11.504] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 09/14/2023] [Accepted: 10/26/2023] [Indexed: 11/22/2023] Open
Abstract
BACKGROUND Pancreatic cancer is difficult to be diagnosed early clinically, while often leads to poor prognosis. If optimal personalized treatment plan can be provided to pancreatic cancer patient at an earlier stage, this can greatly improve overall survival (OS). Circulating tumor cells (CTCs) are a collective term for various types of tumor cells present in the peripheral blood (PB), which are formed by detachment during the development of solid tumor lesions. Most CTCs undergo apoptosis or are phagocytosed after entering the PB, whereas a few can escape and anchor at distal sites to develop metastasis, increasing the risk of death for patients with malignant tumors. AIM To investigate the significance of CTCs in predicting the prognosis of early pancreatic cancer patients. METHODS The PubMed, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure, China Biology Medicine, and ChinaInfo databases were searched for articles published through December 2022. Studies were considered qualified if they included patients with early pancreatic cancer, analyzed the prognostic value of CTCs, and were full papers reported in English or Chinese. Researches were selected and assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol and the Newcastle-Ottawa Scale criteria. We used a funnel plot to assess publication bias. RESULTS From 1595 publications, we identified eight eligible studies that collectively enrolled 355 patients with pancreatic cancer. Among these original studies, two were carried out in China; three in the United States; and one each in Italy, Spain, and Norway. All eight studies analyzed the relevance between CTCs and the prognosis of patients with early-stage pancreatic cancer after surgery. A meta-analysis showed that the patients that were positive pre-treatment or post-treatment for CTCs were associated with decreased OS [hazard ratio (HR) = 1.93, 95% confidence interval (CI): 1.197-3.126, P = 0.007] and decreased relapse-free/disease-free/progression-free survival (HR = 1.27, 95%CI: 1.137-1.419, P < 0.001) in early-stage pancreatic cancer. Additionally, the results suggest no statistically noticeable publication bias for overall, disease-free, progression-free, and recurrence-free survival. CONCLUSION This pooled meta-analysis shows that CTCs, as biomarkers, can afford reliable prognostic information for patients with early-stage pancreatic cancer and help develop individualized treatment plans.
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Affiliation(s)
- Zi-Han Zhang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Yi-Wen Bao
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Ya-Jun Zhao
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Jian-Quan Wang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Jin-Tao Guo
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Si-Yu Sun
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
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Matsuoka T, Yashiro M. Novel biomarkers for early detection of gastric cancer. World J Gastroenterol 2023; 29:2515-2533. [PMID: 37213407 PMCID: PMC10198055 DOI: 10.3748/wjg.v29.i17.2515] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 01/31/2023] [Accepted: 04/13/2023] [Indexed: 05/23/2023] Open
Abstract
Gastric cancer (GC) remains a leading cause of cancer-related death worldwide. Less than half of GC cases are diagnosed at an advanced stage due to its lack of early symptoms. GC is a heterogeneous disease associated with a number of genetic and somatic mutations. Early detection and effective monitoring of tumor progression are essential for reducing GC disease burden and mortality. The current widespread use of semi-invasive endoscopic methods and radiologic approaches has increased the number of treatable cancers: However, these approaches are invasive, costly, and time-consuming. Thus, novel molecular noninvasive tests that detect GC alterations seem to be more sensitive and specific compared to the current methods. Recent technological advances have enabled the detection of blood-based biomarkers that could be used as diagnostic indicators and for monitoring postsurgical minimal residual disease. These biomarkers include circulating DNA, RNA, extracellular vesicles, and proteins, and their clinical applications are currently being investigated. The identification of ideal diagnostic markers for GC that have high sensitivity and specificity would improve survival rates and contribute to the advancement of precision medicine. This review provides an overview of current topics regarding the novel, recently developed diagnostic markers for GC.
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Affiliation(s)
- Tasuku Matsuoka
- Molecular Oncology and Therapeutics, Osaka Metropolitan University Graduate School of Medicine, Osaka 5458585, Japan
| | - Masakazu Yashiro
- Molecular Oncology and Therapeutics, Osaka Metropolitan University Graduate School of Medicine, Osaka 5458585, Japan
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Guo X, Gao Y, Song Q, Wei J, Wu J, Dong J, Chen L, Xu S, Wu D, Yang X, Chen L, Li X, Ji G, Lv X, Wei B. Early assessment of circulating exosomal lncRNA-GC1 for monitoring neoadjuvant chemotherapy response in gastric cancer. Int J Surg 2023; 109:1094-1104. [PMID: 37222716 PMCID: PMC10389467 DOI: 10.1097/js9.0000000000000249] [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: 08/08/2022] [Accepted: 01/22/2023] [Indexed: 05/25/2023]
Abstract
BACKGROUND The timing of surgery for patients with gastric cancer (GC) who undergo neoadjuvant chemotherapy (neoCT) was mainly guided by serial radiologic imaging. However, an earlier assessment was indispensable to avoid delayed treatment for nonresponders and excessive toxicity for responders. Our previous study has identified circulating extracellular vesicles-derived lncRNA-GC1 as a biomarker for early detection and monitoring progression of GC. However, the potential role of neoCT remains poorly understood. METHODS In this explorative biomarker analysis, we conducted a multi-cohort study to examine longitudinal levels of circulating extracellular vesicles-derived lncRNA-GC1 in 798 patients enrolled in the RESONANCE study (NCT01583361). Both circulating extracellular vesicles-derived lncRNA-GC1 and traditional gastrointestinal biomarkers were assessed at defined time nodes. Computed tomography (CT) scans were performed before treatment and 8-10 weeks and assessed based on the RECIST criteria. RESULTS Circulating extracellular vesicles-derived lncRNA-GC1 could be detected in 96.3% of patients at baseline, and significant reductions were observed before cycle 2 (P<0.0001). Levels of circulating extracellular vesicles-derived lncRNA-GC1 showed a stronger correlation with tumor burden and exhibited earlier dynamic changes than the traditional gastrointestinal biomarkers during the first cycle of neoCT. Strong agreement was observed between circulating extracellular vesicles-derived lncRNA-GC1 response (reduction >50%) and radiographic response (Cohen's κ, 0.704). Importantly, circulating extracellular vesicles-derived lncRNA-GC1 maintained predictive value in two external cohorts. Patients with circulating extracellular vesicles-derived lncRNA-GC1 response showed superior disease-free survival [hazard ratio (HR), 0.6238; 95% CI, 0.4095-0.9501; P=0.0118] and overall survival (HR, 0.6131; 95% CI, 0.4016-0.9358; P=0.0090). CONCLUSION Circulating extracellular vesicles-derived lncRNA-GC1 is an early marker of neoCT efficacy and predicts superior survival in GC patients treated with neoCT.
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Affiliation(s)
- Xin Guo
- Department of Digestive Surgery
- Department of Endoscopic Surgery, Air Force 986th Hospital, Fourth Military Medical University, Xian
- Department of General Surgery, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Yunge Gao
- Department of Gynecology and Obstetrics
| | - Qiying Song
- Department of General Surgery, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | | | | | - Jian Dong
- Department of Gynecology and Obstetrics
| | | | - Shenhui Xu
- Department of Pathology, Xijing Hospital
| | - Di Wu
- Department of General Surgery, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | | | - Lubin Chen
- Department of Digestive Surgery
- Department of Endoscopic Surgery, Air Force 986th Hospital, Fourth Military Medical University, Xian
| | | | - Gang Ji
- Department of Digestive Surgery
| | | | - Bo Wei
- Department of General Surgery, Chinese PLA General Hospital, Beijing, People’s Republic of China
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Tang SY, Zhou PJ, Meng Y, Zeng FR, Deng GT. Gastric cancer: An epigenetic view. World J Gastrointest Oncol 2022; 14:90-109. [PMID: 35116105 PMCID: PMC8790429 DOI: 10.4251/wjgo.v14.i1.90] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 05/17/2021] [Accepted: 12/23/2021] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) poses a serious threat worldwide with unfavorable prognosis mainly due to late diagnosis and limited therapies. Therefore, precise molecular classification and search for potential targets are required for diagnosis and treatment, as GC is complicated and heterogeneous in nature. Accumulating evidence indicates that epigenetics plays a vital role in gastric carcinogenesis and progression, including histone modifications, DNA methylation and non-coding RNAs. Epigenetic biomarkers and drugs are currently under intensive evaluations to ensure efficient clinical utility in GC. In this review, key epigenetic alterations and related functions and mechanisms are summarized in GC. We focus on integration of existing epigenetic findings in GC for the bench-to-bedside translation of some pivotal epigenetic alterations into clinical practice and also describe the vacant field waiting for investigation.
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Affiliation(s)
- Si-Yuan Tang
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Pei-Jun Zhou
- Cancer Research Institute, School of Basic Medicine Science, Central South University, School of Basic Medicine Science, Central South University 410008, Hunan Province, China
| | - Yu Meng
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Fu-Rong Zeng
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Guang-Tong Deng
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
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Chen D, Ping S, Xu Y, Wang M, Jiang X, Xiong L, Zhang L, Yu H, Xiong Z. Non-Coding RNAs in Gastric Cancer: From Malignant Hallmarks to Clinical Applications. Front Cell Dev Biol 2021; 9:732036. [PMID: 34805143 PMCID: PMC8595133 DOI: 10.3389/fcell.2021.732036] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 10/18/2021] [Indexed: 01/19/2023] Open
Abstract
Gastric cancer (GC) is one of the most lethal malignancies worldwide. However, the molecular mechanisms underlying gastric carcinogenesis remain largely unknown. Over the past decades, advances in RNA-sequencing techniques have greatly facilitated the identification of various non-coding RNAs (ncRNAs) in cancer cells, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Accumulating evidence has revealed that ncRNAs are essential regulators in GC occurrence and development. However, ncRNAs represent an emerging field of cancer research, and their complex functionality remains to be clarified. Considering the lack of viable biomarkers and therapeutic targets in GC, further studies should focus on elucidating the intricate relationships between ncRNAs and GC, which can be translated into clinical practice. In this review, we summarize recent research progress on how ncRNAs modulate the malignant hallmarks of GC, especially in tumor immune escape, drug resistance, and stemness. We also discuss the promising applications of ncRNAs as diagnostic biomarkers and therapeutic targets in GC, aiming to validate their practical value for clinical treatment.
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Affiliation(s)
- Di Chen
- Department of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shuai Ping
- Department of Orthopaedics, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yushuang Xu
- Department of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Mengmeng Wang
- Department of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xin Jiang
- Department of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lina Xiong
- Department of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Li Zhang
- Department of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Honglu Yu
- Department of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhifan Xiong
- Department of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Yao L, Xie Y. Down-regulation of hsa_circ_0006470 predicts tumor invasion: A new biomarker of gastric cancer. J Clin Lab Anal 2021; 35:e23879. [PMID: 34165822 PMCID: PMC8373341 DOI: 10.1002/jcla.23879] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Revised: 05/28/2021] [Accepted: 06/06/2021] [Indexed: 12/14/2022] Open
Abstract
Background Gastric cancer (GC) is a common cancer. Circular RNAs (circRNAs) regulate the pathogenesis of GC. This study aims to explore its potential as a GC biomarker. Methods The expression of hsa_circ_0006470 in GC tissues and GC cell lines was measured by quantitative reverse transcription‐polymerase chain reaction. The diagnostic value of hsa_circ_0006470 was estimated by the receiver operating characteristic (ROC) curve. Results Compared with adjacent normal tissues, the expression of hsa_circ_0006470 in GC tissues was significantly lower. The expression levels of hsa_circ_0006470 in different TNM stages and different invasion degrees were significantly different. The area under the ROC curve was 0.783, with sensitivity and specificity 0.725 and 0.750, respectively. Conclusions Hsa_circ_0006470 has a high value as a diagnostic biomarker for GC.
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Affiliation(s)
- Lipeng Yao
- Ningbo College of Health Sciences, Ningbo, Zhejiang, China.,Zhejiang Key Laboratory of Pathophysiology, Department of Biochemistry and Molecular Biology, Medical School of Ningbo University, Ningbo, Zhejiang, China
| | - Yaoyao Xie
- Zhejiang Key Laboratory of Pathophysiology, Department of Biochemistry and Molecular Biology, Medical School of Ningbo University, Ningbo, Zhejiang, China
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Liang W, Xia B, Yan M, Zhai G, Li M. Enhanced LINC01061 Levels as a Serum Biomarker in Gastric Cancer and Promotion of Malignant Transformation. Oncol Res Treat 2021; 44:242-251. [PMID: 33910210 DOI: 10.1159/000508310] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2019] [Accepted: 04/29/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND The genomic copy number of LINC01061 is amplified in papillary thyroid cancer. However, its role in gastric cancer is not clear. MATERIALS AND METHODS Tissues and serum of GC patients were collected to detect the expression of LINC01061 by quantitative real-time polymerase chain reaction (qRT-PCR). ShRNA were applied to knock down the expression of LINC01061. Growth curves and colony formation experiments were applied to evaluate cell growth. Cell migration was assessed by transwell migration experiments. Cell cycle and apoptosis were analyzed by flow cytometry. Epithelial-mesenchymal transition (EMT) was examined by qRT-PCR and Western blot. RESULTS The expression of LINC01061 was upregulated in tissues and serum of GC patients and it was associated with the clinicopathological features and survival time. Functional study indicated that cell growth and migration were suppressed after LINC01061 knockdown. Cell cycle arrest and increased apoptosis occurred when LINC01061 expression was inhibited. EMT was also impaired combined with a decrease in β-catenin expression after LINC01061 knockdown. CONCLUSIONS Our data indicate that LINC01061 is a novel biomarker for diagnosis and prognosis of GC. LINC01061 promoted progression of GC through cell cycle regulation and EMT.
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Affiliation(s)
- Wei Liang
- Department of Laboratory Medicine, Nanjing Medical University Affiliated Suzhou Hospital North, Suzhou, China
| | - Bin Xia
- Department of Laboratory Medicine, Suzhou Science and Technology Town Hospital, Nanjing Medical University Affiliated Suzhou Hospital West, Suzhou, China
| | - Meina Yan
- Department of Laboratory Medicine, Nanjing Medical University Affiliated Suzhou Hospital North, Suzhou, China
| | - Guanghua Zhai
- Department of Laboratory Medicine, Nanjing Medical University Affiliated Suzhou Hospital North, Suzhou, China
| | - Meifen Li
- Department of Laboratory Medicine, Nanjing Medical University Affiliated Suzhou Hospital North, Suzhou, China
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Liu R, Li Y, Wu A, Kong M, Ding W, Hu Z, Chen L, Cai W, Wang F. Identification of Plasma hsa_circ_0005397 and Combined With Serum AFP, AFP-L3 as Potential Biomarkers for Hepatocellular Carcinoma. Front Pharmacol 2021; 12:639963. [PMID: 33679420 PMCID: PMC7933497 DOI: 10.3389/fphar.2021.639963] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 01/19/2021] [Indexed: 12/13/2022] Open
Abstract
Background: Mounting evidence has demonstrated that circular RNA (circRNA) plays crucial roles in the occurrence and development of hepatocellular carcinoma (HCC). However, the expression pattern and clinical application value of plasma circRNA in HCC are still largely unknown. Herein, we explored the role of plasma hsa_circ_0005397 in diagnosis and prognosis of HCC. Methods: The expression level of plasma hsa_circ_0005397 was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The identification and origin of plasma hsa_circ_0005397 were confirmed by RNase R assay, Sanger sequencing and HCC cell culture. In addition, its diagnostic value was assessed by receiver operating characteristic (ROC) curve and prognostic value was evaluated by dynamics monitoring and Kaplan–Meier curve analyses in HCC patients. Results: The expression of plasma hsa_circ_0005397 was higher in patients with HCC than that in patients with benign liver diseases and healthy controls (both p < 0.05). Moreover, it was closely correlated with tumor size (p = 0.020) and TNM stage (p = 0.006) of HCC patients. The area under the ROC curve of plasma hsa_circ_0005397 was 0.737 and 95% confidence interval was 0.671–0.795. Furthermore, the combination of plasma hsa_cic_0005397, serum AFP and AFP-L3 could improve the diagnostic sensitivity of HCC. Additionally, dynamic monitoring plasma hsa_cic_0005397 might help us predict recurrence or metastasis in HCC patients after surgical resection. Besides, the increased plasma hsa_cic_0005397 was closely correlated with shorter overall survival of HCC patients (p = 0.007). Conclusion: Plasma has_circ_0005397 represents a novel noninvasive biomarker for HCC. Moreover, the combination of plasma hsa_cic_0005397, serum AFP and AFP-L3 might improve the diagnostic value for HCC.
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Affiliation(s)
- Ruoyu Liu
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Jiangsu, China
| | - Yi Li
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Jiangsu, China
| | - Anqi Wu
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Jiangsu, China
| | - Mingzhu Kong
- Department of Laboratory Medicine, School of Public Health, Nantong University, Jiangsu, China
| | - Weijia Ding
- Department of Laboratory Medicine, School of Public Health, Nantong University, Jiangsu, China
| | - Zeyang Hu
- Department of Laboratory Medicine, School of Public Health, Nantong University, Jiangsu, China
| | - Lin Chen
- Department of Gastroenterology and Laboratory Medicine, Nantong Third Hospital Affiliated to Nantong University, Jiangsu, China
| | - Weihua Cai
- Department of Gastroenterology and Laboratory Medicine, Nantong Third Hospital Affiliated to Nantong University, Jiangsu, China
| | - Feng Wang
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Jiangsu, China
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Jing R, Liu S, Jiang Y, Zong W, Ju S, Cui M. Determination of serum RP11-731F5.2 as a noninvasive biomarker for gastric cancer diagnosis and prognosis. Pathol Res Pract 2020; 216:153261. [DOI: 10.1016/j.prp.2020.153261] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 10/16/2020] [Accepted: 10/17/2020] [Indexed: 12/12/2022]
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Fang X, Wang D, Pu K, Zhang Z, Wang H, Wang H, Zheng Y, Wang Y, Guan Q, Zhou Y. Diagnostic value of circulating lncRNAs as biomarkers of digestive system cancers: A systematic review and meta-analysis. Expert Rev Mol Diagn 2020; 20:1051-1062. [PMID: 33138648 DOI: 10.1080/14737159.2020.1822169] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2020] [Accepted: 09/08/2020] [Indexed: 12/23/2022]
Abstract
OBJECTIVE This meta-analysis aims to explore the diagnostic value and accuracy of circulating lncRNAs as biomarkers of digestive system tumors. METHODS PubMed, Embase, Cochrane Library, and Web of science were searched for relevant articles that were published before April 2019, and a meta-analysis was conducted. RESULTS 52 studies with 63 lncRNAs were discussed in the meta-analysis. The pooled sensitivity and specificity of diagnosis were 0.80 (95% CI: 0.79-0.81) and 0.76 (95% CI: 0.75-0.77), respectively. The pooled DOR (the diagnostic odds ratio) was 15.63 (95% CI: 12.77-19.12), and the overall AUC (the area under the curve) was 0.87. Besides, subgroup analyzes showed that the DOR and AUC of large sample sizes (>80), multiple lncRNAs, serum-based lncRNAs, and downregulation group were superior to those of small sample sizes (≤80), single lncRNA, plasma-based lncRNAs, and upregulation group, respectively. The current data also highlight that the diagnostic accuracy of circulating lncRNAs in the case of colorectal cancer was higher than gastric cancer, hepatocellular carcinoma, esophageal carcinoma, and pancreatic cancer. And there is no difference in the perspective of geographical regions. CONCLUSION The circulating lncRNAs have high diagnostic value and accuracy in digestive system cancers and may serve as potential biomarkers.
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Affiliation(s)
- Xidong Fang
- The First Clinical Medical College, Lanzhou University , Lanzhou, China
- Department of Gastroenterology, The First Hospital of Lanzhou University , Lanzhou, China
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University , Lanzhou, China
| | - Dongke Wang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Ke Pu
- The First Clinical Medical College, Lanzhou University , Lanzhou, China
- Department of Gastroenterology, The First Hospital of Lanzhou University , Lanzhou, China
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University , Lanzhou, China
| | - Zhaoyu Zhang
- Department of Physiology and Pathophysiology, Peking University Health Science Center , Beijing, China
| | - Huiying Wang
- Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University , Changsha, Hunan, China
- National Clinical Research Center for Metabolic Diseases , Changsha, Hunan, China
| | - Haojia Wang
- The First Clinical Medical College, Lanzhou University , Lanzhou, China
| | - Ya Zheng
- The First Clinical Medical College, Lanzhou University , Lanzhou, China
- Department of Gastroenterology, The First Hospital of Lanzhou University , Lanzhou, China
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University , Lanzhou, China
| | - Yuping Wang
- The First Clinical Medical College, Lanzhou University , Lanzhou, China
- Department of Gastroenterology, The First Hospital of Lanzhou University , Lanzhou, China
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University , Lanzhou, China
| | - Quanlin Guan
- The First Clinical Medical College, Lanzhou University , Lanzhou, China
- Department of Oncology Surgery, The First Hospital of Lanzhou University , Lanzhou, China
| | - Yongning Zhou
- The First Clinical Medical College, Lanzhou University , Lanzhou, China
- Department of Gastroenterology, The First Hospital of Lanzhou University , Lanzhou, China
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University , Lanzhou, China
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Tang Z, Huang J, He H, Ma C, Wang K. Contributing to liquid biopsy: Optical and electrochemical methods in cancer biomarker analysis. Coord Chem Rev 2020. [DOI: 10.1016/j.ccr.2020.213317] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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16
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Yuan L, Xu ZY, Ruan SM, Mo S, Qin JJ, Cheng XD. Long non-coding RNAs towards precision medicine in gastric cancer: early diagnosis, treatment, and drug resistance. Mol Cancer 2020; 19:96. [PMID: 32460771 PMCID: PMC7251695 DOI: 10.1186/s12943-020-01219-0] [Citation(s) in RCA: 219] [Impact Index Per Article: 43.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Accepted: 05/21/2020] [Indexed: 02/07/2023] Open
Abstract
Gastric cancer is a deadly disease and remains the third leading cause of cancer-related death worldwide. The 5-year overall survival rate of patients with early-stage localized gastric cancer is more than 60%, whereas that of patients with distant metastasis is less than 5%. Surgical resection is the best option for early-stage gastric cancer, while chemotherapy is mainly used in the middle and advanced stages of this disease, despite the frequently reported treatment failure due to chemotherapy resistance. Therefore, there is an unmet medical need for identifying new biomarkers for the early diagnosis and proper management of patients, to achieve the best response to treatment. Long non-coding RNAs (lncRNAs) in body fluids have attracted widespread attention as biomarkers for early screening, diagnosis, treatment, prognosis, and responses to drugs due to the high specificity and sensitivity. In the present review, we focus on the clinical potential of lncRNAs as biomarkers in liquid biopsies in the diagnosis and prognosis of gastric cancer. We also comprehensively discuss the roles of lncRNAs and their molecular mechanisms in gastric cancer chemoresistance as well as their potential as therapeutic targets for gastric cancer precision medicine.
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Affiliation(s)
- Li Yuan
- The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006 China
| | - Zhi-Yuan Xu
- Institute of Cancer and Basic Medicine, Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Banshan Road 1#, Gongshu District, Hangzhou, 310022 China
| | - Shan-Ming Ruan
- The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006 China
| | - Shaowei Mo
- The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006 China
| | - Jiang-Jiang Qin
- Institute of Cancer and Basic Medicine, Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Banshan Road 1#, Gongshu District, Hangzhou, 310022 China
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, 548 Binwen Road, Binjiang District, Hangzhou, 310053 China
| | - Xiang-Dong Cheng
- Institute of Cancer and Basic Medicine, Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Banshan Road 1#, Gongshu District, Hangzhou, 310022 China
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Zheng P, Zhang H, Gao H, Sun J, Li J, Zhang X, Gao L, Ma P, Li S. Plasma Exosomal Long Noncoding RNA lnc-SLC2A12-10:1 as a Novel Diagnostic Biomarker for Gastric Cancer. Onco Targets Ther 2020; 13:4009-4018. [PMID: 32494155 PMCID: PMC7227815 DOI: 10.2147/ott.s253600] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Accepted: 04/23/2020] [Indexed: 12/13/2022] Open
Abstract
Purpose Exosomes participate in cellular communications by transmitting active molecules, including long noncoding RNAs (lncRNAs) and are regarded as suitable candidates for disease diagnosis. This study aimed to identify gastric cancer (GC)-specific exosomal lncRNA and investigate the potential diagnostic value of plasma exosomal lncRNA in GC. Patients and Methods Exosomes from the culture media (CM) of four GC cells (GCCs) and human gastric epithelial cells were isolated. Exosomal RNA was extracted, and lncRNA microarray assay was performed to identify GC-specific exosomal lncRNAs. The expression levels of the candidate exosomal lncRNAs were validated in 120 subjects via quantitative reverse transcription PCR (qRT-PCR). The receiver operating characteristic (ROC) curve and area under curve were used to estimate the diagnostic capacity. We investigated the potential relationship between plasma exosomal lncRNA expression and the clinicopathological parameters of GC. Results A total of 199 exosomal lncRNAs were expressed at considerable higher levels in GCCs than those in normal controls, among which the top 10 upregulated lncRNAs were selected for further validation in cell, CM, and plasma. qRT-PCR revealed that lnc-SLC2A12-10:1 was remarkably upregulated in exosomes derived from patients with GC and GCCs. The area under the ROC curve was 0.776, which was higher than the diagnostic accuracies of CEA, CA 19-9, and CA72-4. The expression level of exosomal lnc-SLC2A12-10:1 was also significantly correlated with tumor size, TNM stage, lymph node metastasis, and degree of differentiation. The postoperative expression levels of exosomal lnc-SLC2A12-10:1 were lower compared with those of preoperative levels. Conclusion Our study suggested that exosomal lnc-SLC2A12-10:1 may be a potential noninvasive biomarker for the diagnosis and prognosis monitoring of GC. Further large-scale studies are necessary to validate its performance in GC progression.
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Affiliation(s)
- Peiming Zheng
- Department of Clinical Laboratory, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, People's Republic of China
| | - Haoliang Zhang
- Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, People's Republic of China
| | - Huijie Gao
- Department of Oncology, The First Affiliated Hospital of Henan University, Kaifeng 450001, People's Republic of China
| | - Jingfang Sun
- Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, People's Republic of China
| | - Junmeng Li
- Department of Gastrointestinal Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, People's Republic of China
| | - Xiulei Zhang
- Department of Microbiome Laboratory, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, People's Republic of China
| | - Lan Gao
- Department of Clinical Laboratory, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, People's Republic of China
| | - Ping Ma
- Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, People's Republic of China.,Medical Technology School of Xuzhou Medical University, Xuzhou 221004, People's Republic of China
| | - Shibao Li
- Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, People's Republic of China.,Medical Technology School of Xuzhou Medical University, Xuzhou 221004, People's Republic of China
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Zong W, Feng W, Jiang Y, Cao Y, Ke Y, Shi X, Ju S, Cong H, Wang X, Cui M, Jing R. LncRNA CTC-497E21.4 promotes the progression of gastric cancer via modulating miR-22/NET1 axis through RhoA signaling pathway. Gastric Cancer 2020; 23:228-240. [PMID: 31451992 DOI: 10.1007/s10120-019-00998-w] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Accepted: 08/16/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Long non-coding RNAs (lncRNAs) have emerged as important roles in gastric cancer (GC). However, the role of the dysregulated lncRNAs in GC remained large unknown. We investigated the clinical significance, biological function and mechanism of CTC-497E21.4 in GC. METHODS Firstly, RTFQ-PCR was used to detect the expression of CTC-497E21.4 in GC. Furthermore, knockdown of CTC-497E21.4 was conducted to assess the effect of CTC-497E21.4 in vitro and vivo. Subcellular localization of CTC-497E21.4 was determined by nuclear plasmolysis PCR and FISH. We also predicted CTC-497E21.4 binding miRNAs and downstream target genes and evaluated its regulation of miR-22 by acting as a ceRNA. RESULT CTC-497E21.4 was upregulated in GC tissues and GC cell lines (P < 0.05), and the expression was associated with depth of invasion, lymph node metastasis, and neurological invasion. Besides, knockdown of CTC-497E21.4 inhibited cell proliferation, invasion and promoted cell cycle arrest in vitro and inhibited tumorigenesis in vivo. Mechanistic investigations indicated that CTC-497E21.4 acted as a ceRNA for miR-22 and regulated NET1 expression. CTC-497E21.4/miR-22-3p/NET1 participated in the RhoA signaling pathway in the GC progression. CONCLUSION CTC-497E21.4 competed with miR-22 to regulate the expression of NET1 and regulated the malignant progression of GC through RhoA signaling pathway.
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Affiliation(s)
- Wei Zong
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, No 20, Xisi Road, Nantong, 226001, China
| | - Wei Feng
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, No 20, Xisi Road, Nantong, 226001, China
| | - Yun Jiang
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, No 20, Xisi Road, Nantong, 226001, China
| | - Yaning Cao
- School of Public Health, Nantong University, Nantong, China
| | - Yuchen Ke
- School of Public Health, Nantong University, Nantong, China
| | - Xin Shi
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, No 20, Xisi Road, Nantong, 226001, China
| | - Shaoqing Ju
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, No 20, Xisi Road, Nantong, 226001, China
| | - Hui Cong
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, No 20, Xisi Road, Nantong, 226001, China
| | - Xudong Wang
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, No 20, Xisi Road, Nantong, 226001, China
| | - Ming Cui
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, No 20, Xisi Road, Nantong, 226001, China.
| | - Rongrong Jing
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, No 20, Xisi Road, Nantong, 226001, China.
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19
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Zheng J, Ye X, Liu Y, Zhao Y, He M, Xiao H. The combination of CTCs and CEA can help guide the management of patients with SPNs suspected of being lung cancer. BMC Cancer 2020; 20:106. [PMID: 32041568 PMCID: PMC7011271 DOI: 10.1186/s12885-020-6524-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Accepted: 01/08/2020] [Indexed: 12/15/2022] Open
Abstract
Objective Solitary pulmonary nodules (SPNs) is a common radiographic finding and require further evaluation because of the possibility of lung cancer. This study aimed to determine the sensitivity and specificity of circulating tumour cells (CTCs) as a marker for the diagnosis of SPNs and the integration of CTCs, carcinoembryonic antigen (CEA) and imaging findings to improve the sensitivity and specificity of diagnosis in patients with SPNs suspected of being lung cancer. Method For the serum biomarker assay, the concentration of CEA was measured by an automated electrochemiluminescence analyzer. CTCs were collected from 6 ml of blood by the SE i-FISH method, which detects the gene copy number in eight chromosomes and the tumour-associated antigen CK18. Results With a threshold of 6 CTC units, the method showed a sensitivity of 67.1% and a specificity of 56.5% in the diagnosis of NSCLC, especially in the upper lobe, in which the diagnostic strength was the highest (P < 0.01). CTCs, CEA and nodule type had the highest diagnostic efficacy (area under the curve, 0.827; 95% confidence interval, 0.752–0.901) in patients with SPNs being suspected lung cancer. Combining CTCs (cut-off value 12 units) with CEA (1.78 ng/ml), the method showed a sensitivity of 77.8% and a specificity of 90% in the diagnosis of NSCLC, especially in the upper lobe, subsolid nodules and nodules ≥8 mm. Conclusions Our results demonstrated that CTCs are feasible diagnostic biomarkers in patients with SPNs, especially in the upper lobe. Furthermore, CTCs combined with CEA showed higher diagnostic efficacy in the upper lobe, subsolid nodules and nodules ≥8 mm.
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Affiliation(s)
- Jian Zheng
- Department of Thoracic Surgery, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China
| | - Xiong Ye
- College of Clinical Medicine, Shanghai University of Medicine & Health Science, Shanghai, China
| | - Yanan Liu
- Department of Clinical Laboratory, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai, China
| | - Yuxia Zhao
- College of Clinical Medicine, Shanghai University of Medicine & Health Science, Shanghai, China
| | - Mudan He
- Department of Respiratory and Critical Care Medicine, Shanghai First Hospital of Baoshan Branch, Shanghai, China
| | - Hui Xiao
- Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiaotong University, 85Wujin Road, Shanghai, 200080, China.
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Liu W, Li Y, Zhang Y, Shen X, Su Z, Chen L, Cai W, Wang F, Ju S. Circulatinglong non-coding RNA FEZF1-AS1 and AFAP1-AS1 serve as potential diagnostic biomarkers for gastric cancer. Pathol Res Pract 2020; 216:152757. [DOI: 10.1016/j.prp.2019.152757] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2019] [Revised: 11/04/2019] [Accepted: 11/17/2019] [Indexed: 12/19/2022]
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21
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Tang X, Zhu J, Liu Y, Chen C, Liu T, Liu J. Current Understanding of Circular RNAs in Gastric Cancer. Cancer Manag Res 2019; 11:10509-10521. [PMID: 31853202 PMCID: PMC6916696 DOI: 10.2147/cmar.s223204] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2019] [Accepted: 11/15/2019] [Indexed: 12/11/2022] Open
Abstract
Gastric cancer (GC) is the third most common cause of cancer-related death worldwide. Advanced diagnosis and high rates of relapse and metastasis are associated with the poor prognosis of this disease. GC has a complex etiopathogenesis of which the underlying mechanisms remain to be explored. Studies on circular RNAs (circRNAs), noncoding RNAs that may be potential targets in GC, have made substantial progress over the past few years. CircRNAs exert important effects on the onset and progression of GC. Hence, this article aims to summarize the findings of recent studies of circRNAs related to GC and to describe the underlying mechanisms and potential applications. The findings indicate that circRNAs participate in GC regulation, proliferation, invasion, and metastasis through regulating microRNAs, proteins, genes, and signaling pathways. In addition, dysregulated circRNAs may be used as novel diagnostic and prognostic biomarkers or therapeutic targets. This review is expected to facilitate a better understanding of GC, and it suggests novel circRNA-based methods to inhibit or prevent GC.
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Affiliation(s)
- Xiaohuan Tang
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Jilin University, Changchun, Jilin, People's Republic of China
| | - Jiaming Zhu
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Jilin University, Changchun, Jilin, People's Republic of China
| | - Yuanda Liu
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Jilin University, Changchun, Jilin, People's Republic of China
| | - Chao Chen
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Jilin University, Changchun, Jilin, People's Republic of China
| | - Tianzhou Liu
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Jilin University, Changchun, Jilin, People's Republic of China
| | - Jingjing Liu
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Jilin University, Changchun, Jilin, People's Republic of China
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Pardini B, Sabo AA, Birolo G, Calin GA. Noncoding RNAs in Extracellular Fluids as Cancer Biomarkers: The New Frontier of Liquid Biopsies. Cancers (Basel) 2019; 11:E1170. [PMID: 31416190 PMCID: PMC6721601 DOI: 10.3390/cancers11081170] [Citation(s) in RCA: 136] [Impact Index Per Article: 22.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Revised: 08/04/2019] [Accepted: 08/10/2019] [Indexed: 02/06/2023] Open
Abstract
The last two decades of cancer research have been devoted in two directions: (1) understanding the mechanism of carcinogenesis for an effective treatment, and (2) improving cancer prevention and screening for early detection of the disease. This last aspect has been developed, especially for certain types of cancers, thanks also to the introduction of new concepts such as liquid biopsies and precision medicine. In this context, there is a growing interest in the application of alternative and noninvasive methodologies to search for cancer biomarkers. The new frontiers of the research lead to a search for RNA molecules circulating in body fluids. Searching for biomarkers in extracellular body fluids represents a better option for patients because they are easier to access, less painful, and potentially more economical. Moreover, the possibility for these types of samples to be taken repeatedly, allows a better monitoring of the disease progression or treatment efficacy for a better intervention and dynamic treatment of the patient, which is the fundamental basis of personalized medicine. RNA molecules, freely circulating in body fluids or packed in microvesicles, have all the characteristics of the ideal biomarkers owing to their high stability under storage and handling conditions and being able to be sampled several times for monitoring. Moreover, as demonstrated for many cancers, their plasma/serum levels mirror those in the primary tumor. There are a large variety of RNA species noncoding for proteins that could be used as cancer biomarkers in liquid biopsies. Among them, the most studied are microRNAs, but recently the attention of the researcher has been also directed towards Piwi-interacting RNAs, circular RNAs, and other small noncoding RNAs. Another class of RNA species, the long noncoding RNAs, is larger than microRNAs and represents a very versatile and promising group of molecules which, apart from their use as biomarkers, have also a possible therapeutic role. In this review, we will give an overview of the most common noncoding RNA species detectable in extracellular fluids and will provide an update concerning the situation of the research on these molecules as cancer biomarkers.
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Affiliation(s)
- Barbara Pardini
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
- Department of Medical Sciences, University of Turin, 10124 Turin, Italy.
- Unit of Molecular Epidemiology and Exposome, Italian Institute for Genomic Medicine (IIGM), 10126 Turin, Italy.
| | - Alexandru Anton Sabo
- Department of Pediatrics, Marie Curie Emergency Clinical Hospital for Children, 077120 Bucharest, Romania
| | - Giovanni Birolo
- Department of Medical Sciences, University of Turin, 10124 Turin, Italy
- Unit of Molecular Epidemiology and Exposome, Italian Institute for Genomic Medicine (IIGM), 10126 Turin, Italy
| | - George Adrian Calin
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
- Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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Feng W, Ding Y, Zong W, Ju S. Non-coding RNAs in regulating gastric cancer metastasis. Clin Chim Acta 2019; 496:125-133. [PMID: 31276633 DOI: 10.1016/j.cca.2019.07.003] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Revised: 07/01/2019] [Accepted: 07/01/2019] [Indexed: 12/12/2022]
Abstract
Gastric cancer is one of the leading causes of cancer-related deaths worldwide, and mortality remains high, especially in East Asia. At present, the main method to diagnose gastric cancer is pathological biopsy. At the time of diagnosis, most patients have been diagnosed with advanced cancer and metastasis. The treatment of gastric cancer patients is mainly radical surgical resection and chemoradiotherapy, while patients with metastatic tumor have great challenges to radical surgery and are prone to drug resistance. Metastasis is an important factor affecting tumor development. In addition, evidence accumulated in the literature indicates that non-coding RNA plays a key role in tumor metastasis. This article reviews the role of ncRNAs in gastric cancer metastasis and discusses the regulatory mechanism in the development and treatment of gastric cancer.
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Affiliation(s)
- Wei Feng
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China
| | - Ye Ding
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China
| | - Wei Zong
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China
| | - Shaoqing Ju
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China.
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Liu Y, Zhang YM, Ma FB, Pan SR, Liu BZ. Long noncoding RNA HOXA11-AS promotes gastric cancer cell proliferation and invasion via SRSF1 and functions as a biomarker in gastric cancer. World J Gastroenterol 2019; 25:2763-2775. [PMID: 31235999 PMCID: PMC6580350 DOI: 10.3748/wjg.v25.i22.2763] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Revised: 04/15/2019] [Accepted: 05/03/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Gastric cancer (GC) is the fourth most frequent malignancy all over the world. The diagnosis of GC is challenging and the prognosis of GC is very unfavorable. Accumulating evidence reveals that serum long noncoding RNAs (lncRNAs) can function as biomarkers in various types of cancers, including GC.
AIM To explore the level and molecular mechanism of the lncRNA HOXA11-AS in GC and the diagnostic and prognostic significance of serum HOXA11-AS in GC.
METHODS HOXA11-AS levels in GC tissue, cell lines, and serum samples were measured. The correlation between HOXA11-AS expression and clinicopathological characteristics was analyzed. The role of HOXA11-AS in the diagnosis and prognosis of GC was evaluated. Cell function assays were performed for exploration of the roles of HOXA11-AS in GC cells. Moreover, Western blot was performed to explore the target regulated by HOXA11-AS in GC cells.
RESULTS Up-regulation of HOXA11-AS was found in GC tissues, cell lines, and serum samples. In GC patients, decreased serum HOXA11-AS levels were negatively related with tumor size, TNM stage, and lymph node metastasis. The area under the receiver operating characteristic curve of serum HOXA11-AS in the diagnosis of GC was 0.924 (95%CI: 0.881-0.967; sensitivity, 0.787; specificity 0.978). Results of the Kaplan-Meier survival curves suggested the GC patients with a lower HOXA11-AS level having a better overall survival rate. HOXA11-AS promoted GC cell proliferation and invasion. SRSF1 may be the target regulated by HOXA11-AS in GC cells.
CONCLUSION HOXA11-AS promotes GC cell proliferation and invasion via SRSF1 and may function as a promising marker in GC.
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Affiliation(s)
- Yun Liu
- Department of Operating Room, Binzhou People's Hospital, Binzhou 256610, Shandong Province, China
| | - Yu-Mei Zhang
- Department of Return Visit, Binzhou People's Hospital, Binzhou 256610, Shandong Province, China
| | - Feng-Bo Ma
- Department of Gastroenterology, Binzhou People's Hospital, Binzhou 256610, Shandong Province, China
| | - Su-Rong Pan
- Department of Gastroenterology, Binzhou People's Hospital, Binzhou 256610, Shandong Province, China
| | - Bao-Zhen Liu
- Department of Gastroenterology, Binzhou People's Hospital, Binzhou 256610, Shandong Province, China
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