Clinical and Translational Research
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Feb 27, 2024; 16(2): 289-306
Published online Feb 27, 2024. doi: 10.4240/wjgs.v16.i2.289
Phospholipase A2 enzymes PLA2G2A and PLA2G12B as potential diagnostic and prognostic biomarkers in cholangiocarcinoma
Chen Qiu, Yu-Kai Xiang, Xuan-Bo Da, Hong-Lei Zhang, Xiang-Yu Kong, Nian-Zong Hou, Cheng Zhang, Fu-Zhou Tian, Yu-Long Yang
Chen Qiu, Yu-Kai Xiang, Xuan-Bo Da, Hong-Lei Zhang, Xiang-Yu Kong, Nian-Zong Hou, Cheng Zhang, Yu-Long Yang, Center of Gallbladder Disease, Shanghai East Hospital, Institute of Gallstone Disease, School of Medicine, Tongji University, Shanghai 200092, China
Fu-Zhou Tian, General Surgery Center, Chengdu Military General Hospital, Chengdu 610083, Sichuan Province, China
Author contributions: Yang YL for the design of the study; Zhang C and Tian FZ for review and editing; Da XB, Zhang HL, Kong XY, and Hou NZ for data collection from Gene Expression Omnibus and The Cancer Genome Atlas; Qiu C and Xiang YK for data analysis and drafting of the article.
Supported by the Key Specialty Construction Project of Shanghai Pudong New Area Health Commission, No. PWZzk2022-17; Shanghai East Hospital Clinical Research Project, No. DFLC2022019; and the Featured Clinical Discipline Project of Shanghai Pudong District, No. PWYts2021-06.
Institutional review board statement: The datasets of this study are from The Cancer Genome Atlas and the Gene Expression Omnibus, the institutional review board is not related to this statement.
Clinical trial registration statement: The datasets of this study are from The Cancer Genome Atlas and the Gene Expression Omnibus, the clinical trial registration is not related to this statement.
Informed consent statement: The datasets of this study are from The Cancer Genome Atlas and the Gene Expression Omnibus, the informed consent is not related to this statement.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
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: Yu-Long Yang, Center of Gallbladder Disease, Shanghai East Hospital, Institute of Gallstone Disease, School of Medicine, Tongji University, No. 150 Jimo Road, Shanghai 200092, China. yyl516@tongji.edu.cn
Received: December 1, 2023
Peer-review started: December 1, 2023
First decision: December 7, 2023
Revised: December 19, 2023
Accepted: January 15, 2024
Article in press: January 15, 2024
Published online: February 27, 2024
ARTICLE HIGHLIGHTS
Research background

The study delves into the complex nature of cholangiocarcinoma (CCA), a heterogeneous set of malignancies in the biliary tract. It acknowledges the growing global incidence of CCA, now accounting for a significant portion of primary liver and gastrointestinal cancers. The research examines the role of phospholipase A2 (PLA2) enzymes in CCA, focusing on the differential expression of PLA2G2A and PLA2G12B genes and their potential as prognostic markers. This comprehensive analysis aims to enhance diagnostic and therapeutic strategies for CCA, addressing the complex biology that challenges current treatment approaches.

Research motivation

This study focuses on CCA, a group of complex biliary tract cancers. It aims to unravel the roles of specific PLA2 enzymes, particularly PLA2G2A and PLA2G12B in CCA. The research addresses the challenge of understanding CCA’s diverse genetic landscape and its implications for treatment resistance. Solving these issues could lead to breakthroughs in targeted therapies, improving prognosis and patient outcomes in CCA. This could significantly advance the field, offering insights into the molecular underpinnings of CCA and guiding future research directions.

Research objectives

The main objective of this research was to investigate the roles of PLA2G2A and PLA2G12B in CCA, focusing on their expression patterns and prognostic significance. The study realized these objectives by analyzing extensive bioinformatics data and highlighted the potential of these genes as biomarkers for CCA. Achieving these objectives is significant for future research, as it opens avenues for more targeted therapeutic strategies, improves diagnostic accuracy, and contributes to a better understanding of CCA’s molecular biology, potentially leading to enhanced patient care and outcomes.

Research methods

The study employs advanced bioinformatics and clinical data analysis to explore PLA2G2A and PLA2G12B genes in CCA. Using data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), it integrates gene expression profiling, microRNA (miRNA) analysis, and statistical methods to understand the genes’ roles and prognostic value, offering novel insights for future cancer research and therapy.

Research results

Our study makes significant contributions to the understanding of CCA by examining the gene expression of the PLA2 family and its impact on CCA. We identified specific PLA2G2A and PLA2G12B genes that showed notable expression differences between normal and tumor tissues. These findings were further supported by our exploration of genetic alterations and pathway enrichment analyses. Additionally, we investigated the prognostic value of miRNAs related to these genes, providing new insights into their role in CCA.

Research conclusions

This study introduces a comprehensive bioinformatics analysis of PLA2G2A and PLA2G12B genes in CCA, providing new insights into their roles in cancer progression and prognosis. The methods involve advanced data analysis from databases like TCGA and GEO, emphasizing the significance of these genes in CCA’s molecular pathways. This approach contributes to understanding CCA’s complex biology and highlights potential diagnostic and therapeutic targets.

Research perspectives

Future research should focus on validating the roles of PLA2G2A and PLA2G12B in CCA using clinical samples, expanding sample sizes for a more robust analysis, and conducting in vivo and in vitro experiments. These steps are crucial for understanding the molecular mechanisms of PLA2 in CCA and confirming their potential as diagnostic and therapeutic targets. Additionally, exploring the complex interactions between miRNAs and PLA2 enzymes, and their impact on CCA progression and patient prognosis, should be a priority.