Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 7, 2023; 29(25): 4053-4071
Published online Jul 7, 2023. doi: 10.3748/wjg.v29.i25.4053
Molecular profiling reveals potential targets in cholangiocarcinoma
Dan Liu, Yang Shi, Hongze Chen, Muhammad Azhar Nisar, Nicholas Jabara, Noah Langwinski, Sophia Mattson, Katsuya Nagaoka, Xuewei Bai, Shaolei Lu, Chiung-Kuei Huang
Dan Liu, Yang Shi, Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Hongze Chen, Muhammad Azhar Nisar, Nicholas Jabara, Noah Langwinski, Sophia Mattson, Chiung-Kuei Huang, Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA 70112, United States
Katsuya Nagaoka, Xuewei Bai, Department of Medicine, Rhode Island Hospital and the Alpert Medical School of Brown University, Providence, RI 02903, United States
Shaolei Lu, Department of Pathology, Alpert Medical School of Brown University, Providence, RI 02903, United States
Author contributions: Huang CK contributed to the study concept and design; Liu D, Shi Y, Chen H, Nisar MA, Jabara N, Langwinski N, Mattson S, Nagaoka K, Bai X and Huang CK contributed to the acquisition of data; Liu D, Shi Y, Bai X, Huang CK and Lu S contributed to analysis and interpretation of data; Liu D, Lu S, Jabara N, Nagaoka K, Chen H and Nisar MA contributed to the technical support; Lu S contributed to the material support; Huang CK and Lu S obtained the funding; Liu D, Shi Y, Huang CK, Lu S and Nisar MA drafted the manuscript; Shi Y, Nisar MA, Huang CK, Lu S, Jabara N, Langwinski N and Mattson S revised the manuscript. Liu D and Shi Y contributed equally.
Supported by 2017 AASLD Pinnacle Research Career Development Award.
Institutional review board statement: All protocols were approved by the Institutional Animal Care and Use Committee (IACUC) at Rhode Island Hospital (CMTT # 5051-18), and all experiments were conducted in accordance with the guidelines of this IACUC.
Conflict-of-interest statement: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Chiung-Kuei Huang, PhD, Assistant Professor, Pathology and Laboratory Medicine, Tulane University School of Medicine, 1430 Tulane Ave, New Orleans, LA 70112, United States. chuang17@tulane.edu
Received: January 21, 2023
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
ARTICLE HIGHLIGHTS
Research background

The molecular pathogenesis of cholangiocarcinoma (CCA) remains largely unknown. Investigating the molecular mechanisms underlying CCA progression will potentially yield results toward identifying therapeutic targets.

Research motivation

Several mRNA sequencing (Seq) datasets in CCA samples are publicly available, but it remains unclear if the data can be validated in CCA cell lines, the transgenic CCA mouse model, and human CCA samples.

Research objectives

To summarize the mRNA Seq results and validate the findings in CCA cell lines, the transgenic CCA mouse model, and human CCA samples.

Research methods

Bioinformatic analysis, cell culture studies, transgenic mouse model, human CCA samples, and molecular strategies were used to determine molecular pathogenesis of CCA.

Research results

Through bioinformatic analysis, we found that cell cycle and Notch associated pathways are up-regulated in human CCA samples, compared to the non-tumor controls. We validated the findings in human CCA cell lines and the transgenic CCA mouse model.

Research conclusions

Our data, through mRNA and protein profiling, identified very high similarity between CCA tumors derived from the CCA transgenic mice and human CCA tumors, thus providing a potential preclinical CCA model for investigating CCA tumorigenesis. Besides, our data suggested that cell cycle and Notch associated pathways could be potential therapeutic targets in CCA patients.

Research perspectives

Systemic chemotherapy, gemcitabine and cisplatin, is recommended for CCA patients. However, the 5-year survival of CCA patients has not been significantly improved, suggesting an urgent need to develop novel therapeutic approaches.