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

In the past decades, the potential of microRNA (miRNA) in cancer diagnostics and prognostics has gained a lot of interests. In this study, a meta-analysis was conducted upon the pooled miRNA microarray data of cholangiocarcinoma (CCA).


To identify differentially expressed (DE) miRNAs and perform functional analyses in order to gain insights to understanding miRNA-target interactions involved in tumorigenesis pathways of CCA.


Raw data from 8 CCA miRNA microarray datasets, consisting of 443 samples in total, were integrated and statistically analyzed to identify DE miRNAs via comparison of levels of miRNA expression between CCA and normal bile duct samples using t-tests (P < 0.001). The 10-fold cross validation was performed in order to increase the robustness of the t-test results.


Our data showed 70 up-regulated and 48 down-regulated miRNAs in CCA. Gene Ontology and pathway enrichment analyses revealed that mRNA targets of DE miRNAs were significantly involved in several biological processes. The most prominent dysregulated pathways included phosphatidylinositol-3 kinases/Akt, mitogen-activated protein kinase and Ras signaling pathways.


DE miRNAs found in our meta-analysis revealed dysregulation in major cancer pathways involved in the development of CCA. These results indicated the necessity of understanding the miRNA-target interactions and the significance of dysregulated miRNAs in terms of diagnostics and prognostics of cancers.

Keywords: Cholangiocarcinoma, Microarray, MicroRNA, Meta-analysis

Core tip: At present, there is an accumulating mass of cholangiocarcinoma microRNA (miRNA) profiling data, however, it is challenging to gain the maximal information from these data because the experimental designs in each study tend to focus on only a few specific research questions. This work therefore integrates and inter-validates the cholangiocarcinoma miRNA expression profiles from multiple independent datasets to identify the differential dysregulation of miRNA and their corresponding downstream pathways underlying mechanism of pathogenesis. The significant 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 cholangiocarcinoma development.