Published online Jul 7, 2023. doi: 10.3748/wjg.v29.i25.4053
Peer-review started: January 21, 2023
First decision: February 1, 2023
Revised: February 16, 2023
Accepted: May 23, 2023
Article in press: May 23, 2023
Published online: July 7, 2023
Processing time: 157 Days and 10.4 Hours
Cholangiocarcinoma (CCA) is a devastating malignancy and has a very poor prognosis if tumors spread outside the liver. Understanding the molecular mechanisms underlying the CCA progression will likely yield therapeutic approaches toward treating this deadly disease.
To determine the molecular pathogenesis in CCA progression.
In silico analysis, in vitro cell culture, CCA transgenic animals, histological, and molecular assays were adopted to determine the molecular pathogenesis.
The transcriptomic data of human CCA samples were retrieved from The Cancer Genome Atlas (TGCA, CHOL), European Bioinformatics Institute (EBI, GAD
In summary, our study comprehensively analyzed the gene expression pattern of CCA samples using publicly available datasets and identified the cell cycle and Notch pathways are potential therapeutic targets in this deadly disease.
Core Tip: Molecular profiling of cholangiocarcinoma (CCA) has been conducted using various cohorts. However, the identified targets vary among different cohorts. In the current study, we combined different cohorts of CCA RNA sequencing datasets and refined the potential therapeutic targets in human CCA malignancy. We validated the findings using human CCA cell lines, the KrasG12D and P53 mutation transgenic mouse model, and human CCA clinical data, thus supporting the potential of targeting the identified pathways in clinical trials.