Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Sep 15, 2024; 16(9): 4014-4027
Published online Sep 15, 2024. doi: 10.4251/wjgo.v16.i9.4014
Prognostic value of PEA3 subfamily gene expression in cholangiocarcinoma
Li Wang, Zhe Zhang, Hai-Zhang Ma
Li Wang, Department of Emergency, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
Zhe Zhang, Department of Emergency Medicine, The First People’s Hospital of Linping District Hangzhou, Hangzhou 311100, Zhejiang Province, China
Hai-Zhang Ma, Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250000, Shandong Province, China
Co-corresponding authors: Zhe Zhang and Hai-Zhang Ma.
Author contributions: Wang L analyzed the data and did all the experiments, writing-original drafted the manuscript; Zhang Z designed the project, methodology and funding acquisition; Zhang Z and Ma HZ designed the study, supervised the data collection together; All the authors revised and corrected the manuscript.
Supported by the Science and Technology Development Plan Project of Hangzhou, No. 20201203B56.
Institutional animal care and use committee statement: The feeding process followed the guidelines of the Animal Protection and Use Committee of Zhejiang University of Traditional Chinese Medicine. This study was approved by the Animal Ethics Committee of Zhejiang University of Traditional Chinese Medicine (ethical batch number: IACUC-20230410-21).
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: Not 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: Zhe Zhang, Doctor, Department of Emergency Medicine, The First People’s Hospital of Linping District Hangzhou, No. 369 Yingbin Road, Nanyuan Street, Linping District, Hangzhou 311100, Zhejiang Province, China. zz2516116@163.com
Received: June 21, 2024
Revised: July 19, 2024
Accepted: July 30, 2024
Published online: September 15, 2024
Processing time: 79 Days and 21.3 Hours
Abstract
BACKGROUND

Cholangiocarcinoma (CCA) is a lethal malignancy with limited treatment options and poor prognosis. The PEA3 subfamily of E26 transformation specific genes: ETV1, ETV4, and ETV5 are known to play significant roles in various cancers by influencing cell proliferation, invasion, and metastasis.

AIM

To analyze PEA3 subfamily gene expression levels in CCA and their correlation with clinical parameters to determine their prognostic value for CCA.

METHODS

The expression levels of PEA3 subfamily genes in pan-cancer and CCA data in the cancer genome atlas and genotype-tissue expression project databases were analyzed with R language software. Survival curve and receiver operating characteristic analyses were performed using the SurvMiner, Survival, and Procr language packages. The gene expression profiling interactive analysis 2.0 database was used to analyze the expression levels of PEA3 subfamily genes in different subtypes and stages of CCA. Web Gestalt was used to perform the gene ontology/ Kyoto encyclopedia of genes and genomes (GO/KEGG) analysis, and STRING database analysis was used to determine the genes and proteins related to PEA3 subfamily genes.

RESULTS

ETV1, ETV4, and ETV5 expression levels were significantly increased in CCA. There were significant differences in ETV1, ETV4, and ETV5 expression levels among the different subtypes of CCA, and predictive analysis revealed that only high ETV1 and ETV4 expression levels were significantly associated with shorter overall survival in patients with CCA. GO/KEGG analysis revealed that PEA3 subfamily genes were closely related to transcriptional misregulation in cancer. In vitro and in vivo experiments revealed that PEA3 silencing inhibited the invasion and metastasis of CCA cells.

CONCLUSION

The expression level of ETV4 may be a predictive biomarker of survival in patients with CCA.

Keywords: PEA3 subfamily; Cholangiocarcinoma; The cancer genome atlas; ETV4; The prognosis; Prognostic biomarker

Core Tip: This study investigates the expression of the PEA3 subfamily genes (ETV1, ETV4, ETV5) in cholangiocarcinoma (CCA) and their clinical relevance. Using data from cancer genome atlas and genotype-tissue expression project databases, we identified significantly elevated levels of ETV1, ETV4 and ETV5 in CCA. High expression of ETV1 and ETV4 was explicitly correlated with shorter overall survival in CCA patients. Functional assays demonstrated that silencing PEA3 genes reduces invasion and metastasis in CCA cells in vitro and in vivo. These findings suggest that ETV4 may be a valuable prognostic biomarker for survival of CCA patients.