Retrospective Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jun 16, 2021; 9(17): 4143-4158
Published online Jun 16, 2021. doi: 10.12998/wjcc.v9.i17.4143
Why MUC16 mutations lead to a better prognosis: A study based on The Cancer Genome Atlas gastric cancer cohort
Yu-Jie Huang, Zhi-Fei Cao, Jie Wang, Jian Yang, Yi-Jun Wei, Yu-Chen Tang, Yin-Xiang Cheng, Jian Zhou, Zi-Xiang Zhang
Yu-Jie Huang, Jie Wang, Jian Yang, Yi-Jun Wei, Yu-Chen Tang, Yin-Xiang Cheng, Jian Zhou, Zi-Xiang Zhang, Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
Zhi-Fei Cao, Department of Pathology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu Province, China
Author contributions: Huang YJ and Cao ZF contributed equally to this work; Huang YJ and Cao ZF were responsible for conceptualization, data curation, methodology, and wrote the original draft; Wang J, Yang J, Wei YJ, Tang YC, Cheng YX and Zhou J were responsible for visualization and software; Zhang ZX was responsible for validation, supervision, reviewed and edited the manuscript; all authors approved the final submission.
Supported by National Natural Science Foundation of China, No. 81902385; The Project of Suzhou People's Livelihood Science and Technology, No. SYS2018037 and No. SYS201739; The Six Talent Peaks Project in Jiangsu Province, No. WSW-059; Postgraduate Research & Practice Innovation Program of Jiangsu Province, No. SJCX20_1073; Medical Research Programs of Health Commission Foundation of Jiangsu Province, No. H2019071; and The Project of Medical Research of Jiangsu Province, No. Y2018094 and No. H2018056.
Institutional review board statement: This study was a bioinformatics study, and the data used was downloaded from a public database, so the study did not require the approval of the ethics committee.
Informed consent statement: This research did not involve any human or animal experiments, and the data used was downloaded from a public database, so the study did not require the informed consent.
Conflict-of-interest statement: None declared.
Data sharing statement: No additional data are available.
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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zi-Xiang Zhang, PhD, Associate Professor, Department of General Surgery, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou 215006, Jiangsu Province, China. zixiangzhang@163.com
Received: December 28, 2020
Peer-review started: December 28, 2020
First decision: January 17, 2021
Revised: January 25, 2021
Accepted: March 5, 2021
Article in press: March 5, 2021
Published online: June 16, 2021
Processing time: 149 Days and 8.5 Hours
ARTICLE HIGHLIGHTS
Research background

MUC16 is a frequently mutated gene in gastric cancer and the MUC16 mutations seem to result in a better prognosis in gastric cancer. Unfortunately, the mechanism that leads to a better prognosis with MUC16 mutations is less clear.

Research motivation

Among gastric cancer patients, MUC16 mutations were associated with better prognosis; however, the mechanism of this is not well understood.

Research objectives

To explore in greater depth the underlying mechanisms as to why MUC16 mutations lead to a better prognosis in gastric cancer patients.

Research methods

Based on gastric cancer data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), which were performed to explore the relationship between MUC16 mutations and prognosis, Cox regression and random survival forest algorithms were applied to search for hub genes. Gene set enrichment analysis was used to elucidate the molecular mechanisms. Single sample gene set enrichment analysis and EpiDISH were used to assess immune cells infiltration, and ESTIMATE analyzed the tumor microenvironment.

Research results

Our study shows that MUC16 mutations appear to activate the DNA repair and p53 pathways and act as an anti-tumor agent. We also identified a key gene, NPY1R (neuropeptide Y receptor Y1), with high expression of NPY1R predicting a poorer prognosis, which was confirmed in a separate GEO cohort. Further susceptibility analysis also revealed that NPY1R might be a potential drug target for gastric cancer. In analyzing the tumor microenvironment, we found that immune cells in the mutation group exhibited higher anti-tumor effects. In addition, the tumor mutation burden and cancer stem cells index were also higher in the mutation group.

Research conclusions

By analyzing the gastric cancer data from TCGA and GEO, we speculate that the MUC16 mutation may activate the p53 pathway and DNA repair pathway on the one hand. On the other hand, the tumor microenvironment may be involved, with higher tumor killer cells and lower stromal scores together building the unique tumor microenvironment in the mutation group.

Research perspectives

In gastric cancer patients, MUC16 mutations predict a better prognosis.