Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 7, 2020; 26(29): 4356-4371
Published online Aug 7, 2020. doi: 10.3748/wjg.v26.i29.4356
Dysregulation of microRNA in cholangiocarcinoma identified through a meta-analysis of microRNA profiling
Somsak Likhitrattanapisal, Supeecha Kumkate, Pravech Ajawatanawong, Kanokpan Wongprasert, Rutaiwan Tohtong, Tavan Janvilisri
Somsak Likhitrattanapisal, National Center for Genetic Engineering and Biotechnology, Pathumthani 12120, Thailand
Somsak Likhitrattanapisal, Supeecha Kumkate, Department of Biology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
Pravech Ajawatanawong, Division of Bioinformatics and Data Management for Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
Kanokpan Wongprasert, Department of Anatomy, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
Rutaiwan Tohtong, Tavan Janvilisri, Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
Author contributions: Likhitrattanapisal S and Janvilisri T designed the research; Likhitrattanapisal S and Janvilisri T performed the research; Likhitrattanapisal S, Kumkate S, Ajawatanawong P and Janvilisri T analyzed the data; Wongprasert K, Tohtong R and Janvilisri T facilitated project administration; all authors substantially contributed to the interpretation of data, made critical revisions related to the intellectual content of the manuscript, and approved the final version of the article to be published.
Supported by the Thailand Research Fund, No. DBG5980006; UK-Thailand Research Collaborations (Newton Fund), No. MR/N01247X/1.
Conflict-of-interest statement: The authors declare no conflict of interest.
PRISMA 2009 Checklist statement: This study was written according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Tavan Janvilisri, PhD, Professor, Department of Biochemistry, Faculty of Science, Mahidol University, No. 272, Rama VI Road, Bangkok 10400, Thailand.
Received: December 27, 2019
Peer-review started: December 27, 2019
First decision: February 14, 2020
Revised: May 16, 2020
Accepted: July 22, 2020
Article in press: July 22, 2020
Published online: August 7, 2020
Research background

The incidence of cholangiocarcinoma (CCA) is alarmingly elevating in many countries. Patients with CCA usually have poor prognosis as there is still no effective screening and treatment available. Therefore, it is essential to identify biomarkers for CCA.

Research motivation

Differential expression profiles of microRNA (miRNA) have been reported for many different types of cancer. Thus, a growing number of miRNA microarray data can be a valuable resource for the discovery of biomarkers to tackle challenges in the clinical management of CCA.

Research objectives

This work integrates and intervalidates the CCA miRNA expression profiles from multiple independent datasets to identify the differential dysregulation of miRNA and their corresponding downstream pathways underlying mechanism of pathogenesis.

Research methods

Eight independent CCA miRNA profiling microarray datasets, including 246 CCA and 197 normal samples were assimilated into a meta-analysis and cross-validation to identify a cohort of miRNA that were significantly dysregulated in CCA.

Research results

Of 118 dysregulated miRNA identified in our study, 70 were up-regulated and 48 were down-regulated miRNAs in CCA. Bioinformatic analyses revealed that mRNA targets of differentially expressed miRNAs were significantly distributed across various biological processes. The most prominent dysregulated pathways included phosphatidylinositol-3 kinases/Akt, mitogen-activated protein kinase and Ras signaling pathways.

Research conclusions

This current study represents the meta-analysis of miRNA microarray datasets with highly stringent statistical methodology and provides new insights into the role of miRNA and its dysregulations in CCA.

Research perspectives

The merit of our findings offers a valuable reference for future studies and further investigation of these miRNA/genes and their interactions will eventually lead to the identification of genes and pathways important to the overall mechanism of the dysregulated processes in CCA development.