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      miR-17–92 cluster is connected with disease progression and oxaliplatin/capecitabine chemotherapy efficacy in advanced gastric cancer patients : A preliminary study

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          Abstract

          This study aimed to determine the role of plasma miR-17–92 cluster level in predicting chemoresistance in patients with gastric cancer (GC) undergoing oxaliplatin/capecitabine (XELOX) chemotherapy.

          Patients recently diagnosed with advanced GC were chosen as participants based on the inclusion criteria. The plasma levels of miR-17-5p, miR-18a, miR-19a/b, miR-20a, and miR-92-1 (miR-17–92 cluster) were determined through quantitative RT-PCR of blood samples from GC patients and healthy volunteers. All the patients received XELOX chemotherapy, and the effectiveness of the chemotherapy was evaluated.

          The miR-17–92 plasma level was increased in advanced GC patients and decreased after XELOX chemotherapy. Moreover, the miR-17–92 cluster level was associated with chemotherapy response but not with chemotherapy-related toxicity. The miR-17–92 cluster plasma level was decreased in chemosensitive patients, but not in chemoresistant patients, after chemotherapy. The sensitivity and specificity of the combined detection of the miR-17–92 cluster in patients with advanced GC were 100% each.

          The results suggest that the miR-17–92 plasma level is associated with the progression of advanced GC and effectiveness of XELOX chemotherapy.

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          Differential expression of microRNA species in human gastric cancer versus non-tumorous tissues.

          Bingxiu Xiao, Junming Guo, Yanjun Wang … (2009)
          MicroRNAs (miRNAs) play important roles in carcinogenesis. The global miRNA expression profile of gastric cancer has not been reported. The purpose of the present study was to determine the miRNA expression profile of gastric cancer. Total RNA were first extracted from primary gastric cancer tissues and adjacent non-tumorous tissues and then small isolated RNAs (< 300 nt) were 3'-extended with a poly(A) tail. Hybridization was carried out on a microParaflo microfluidic chip (LC Sciences, Houston, TX, USA). After hybridization detection by fluorescence labeling using tag-specific Cy3 and Cy5 dyes, hybridization images were collected using a laser scanner and digitized using Array-Pro image analysis software (Media Cybernetics, Silver Spring, MD, USA). To validate the results and investigate the biological meaning of differential expressed miRNAs, immunohistochemistry was used to detect the differential expression of target genes. The most highly expressed miRNAs in non-tumorous tissues were miR-768-3p, miR-139-5p, miR-378, miR-31, miR-195, miR-497 and miR-133b. Three of them, miR-139-5p, miR-497 and miR-768-3p, were first found in non-tumorous tissues. The most highly expressed miRNAs in gastric cancer tissues were miR-20b, miR-20a, miR-17, miR-106a, miR-18a, miR-21, miR-106b, miR-18b, miR-421, miR-340*, miR-19a and miR-658. Among them, miR-340*, miR-421 and miR-658 were first found highly expressed in cancer cells. The expression of some target genes (such as Rb and PTEN) in cancer tissues was found to be decreased. To our knowledge, this is the first report about these miRNAs associated with gastric cancer. This new information may suggest the potential roles of these miRNAs in the diagnosis of gastric cancer.
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            MicroRNA profiles in colorectal carcinomas, adenomas and normal colonic mucosa: variations in miRNA expression and disease progression

            Martha Slattery, Jennifer Herrick, Daniel Pellatt … (2016)
            Summary Roughly 27% of miRNAs are commonly expressed in colonic tissue; of these, over 86% are dysregulated between carcinoma and normal tissue when applying a false discovery rate of 0.05. MiRNA expression from normal to adenoma to carcinoma varied by miRNA and its frequency of expression in the population.
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              miRNA signature associated with outcome of gastric cancer patients following chemotherapy

              Chang-Hee Kim, Hark Kim, R Rettig … (2011)
              Background Identification of patients who likely will or will not benefit from cytotoxic chemotherapy through the use of biomarkers could greatly improve clinical management by better defining appropriate treatment options for patients. microRNAs may be potentially useful biomarkers that help guide individualized therapy for cancer because microRNA expression is dysregulated in cancer. In order to identify miRNA signatures for gastric cancer and for predicting clinical resistance to cisplatin/fluorouracil (CF) chemotherapy, a comprehensive miRNA microarray analysis was performed using endoscopic biopsy samples. Methods Biopsy samples were collected prior to chemotherapy from 90 gastric cancer patients treated with CF and from 34 healthy volunteers. At the time of disease progression, post-treatment samples were additionally collected from 8 clinical responders. miRNA expression was determined using a custom-designed Agilent microarray. In order to identify a miRNA signature for chemotherapy resistance, we correlated miRNA expression levels with the time to progression (TTP) of disease after CF therapy. Results A miRNA signature distinguishing gastric cancer from normal stomach epithelium was identified. 30 miRNAs were significantly inversely correlated with TTP whereas 28 miRNAs were significantly positively correlated with TTP of 82 cancer patients (P<0.05). Prominent among the upregulated miRNAs associated with chemosensitivity were miRNAs known to regulate apoptosis, including let-7g, miR-342, miR-16, miR-181, miR-1, and miR-34. When this 58-miRNA predictor was applied to a separate set of pre- and post-treatment tumor samples from the 8 clinical responders, all of the 8 pre-treatment samples were correctly predicted as low-risk, whereas samples from the post-treatment tumors that developed chemoresistance were predicted to be in the high-risk category by the 58 miRNA signature, suggesting that selection for the expression of these miRNAs occurred as chemoresistance arose. Conclusions We have identified 1) a miRNA expression signature that distinguishes gastric cancer from normal stomach epithelium from healthy volunteers, and 2) a chemoreresistance miRNA expression signature that is correlated with TTP after CF therapy. The chemoresistance miRNA expression signature includes several miRNAs previously shown to regulate apoptosis in vitro, and warrants further validation.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Medicine (Baltimore)
                Journal ID (iso-abbrev): Medicine (Baltimore)
                Journal ID (publisher-id): MEDI
                Title: Medicine
                Publisher: Wolters Kluwer Health
                ISSN (Print): 0025-7974
                ISSN (Electronic): 1536-5964
                Publication date Collection: August 2018
                Publication date (Electronic): 21 August 2018
                Volume: 97
                Issue: 35
                Electronic Location Identifier: e12007
                Affiliations
                Department of Oncology, Affiliated Hospital of Qinghai University, Xining, China.
                Author notes
                [∗ ]Correspondence: Yushuang Luo, Department of Oncology, Affiliated Hospital of Qinghai University, No. 29 Tongren Road, Chengxi District, Xining 810001, China (e-mail: luoyushuangys@ 123456163.com ).
                Article
                Publisher ID: MD-D-18-01030 Accession ID: 12007
                DOI: 10.1097/MD.0000000000012007
                PMC ID: 6392796
                PubMed ID: 30170406
                SO-VID: e782b66b-5fe8-4dcf-93e1-2de0461876bb
                Copyright © Copyright © 2018 the Author(s). Published by Wolters Kluwer Health, Inc.
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

                History
                Date received : 6 February 2018
                Date accepted : 30 July 2018
                Categories
                Subject: 4500
                Subject: Research Article
                Subject: Observational Study
                Custom metadata
                OPEN-ACCESS TRUE

                Keywords: chemotherapy,gastric cancer,mir-17–92 cluster,oxaliplatin/capecitabine
                Data availability:
                Keywords: chemotherapy, gastric cancer, mir-17–92 cluster, oxaliplatin/capecitabine

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