Published online Aug 7, 2020. doi: 10.3748/wjg.v26.i29.4356
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
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.
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.
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.
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.
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.
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.
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.