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©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Mar 15, 2023; 15(3): 546-561
Published online Mar 15, 2023. doi: 10.4251/wjgo.v15.i3.546
Mitophagy-related gene signature predicts prognosis, immune infiltration and chemotherapy sensitivity in colorectal cancer
Jin-Sen Weng, Jie-Ping Huang, Wei Yu, Jun Xiao, Fang Lin, Kang-Ni Lin, Wei-Dong Zang, Yong Ye, Jing-Ping Lin
Jin-Sen Weng, Fang Lin, Kang-Ni Lin, Yong Ye, Jing-Ping Lin, Critical Care Medicine, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, Fujian Province, China
Jie-Ping Huang, Department of Emergency, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
Wei Yu, Clinical Pharmacy, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, Fujian Province, China
Jun Xiao, Wei-Dong Zang, Gastrointestinal Surgery Department, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, Fujian Province, China
Author contributions: Weng JS, Huang JP, and Yu W contributed equally to this work; Lin JP and Ye Y had the idea for this study; Weng JS, Huang JP, and Yu W supervised the acquisition of the data; Xiao J and Zang WD undertook the statistical analysis; Lin F, Lin KN, and Zang WD provided statistical advice; all authors contributed to interpretation of the results; Weng JS, Huang JP, and Yu W wrote the article and other authors contributed to the content; all authors approved the final version of the manuscript, including the authorship list.
Institutional review board statement: The study was reviewed and approved by the Fujian Cancer Ethics Committee (Approval No. K2023-030-01).
Informed consent statement: All the data were downloaded from GEO and TCGA database, thus the informed consent statement is not applicable in this study.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: Source data and reagents are available from the corresponding author upon 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: Jing-Ping Lin, MD, Doctor, Critical Care Medicine, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, No. 420 Fuma Road, Fuzhou 350014, Fujian Province, China. ljpccm@163.com
Received: November 20, 2022
Peer-review started: November 20, 2022
First decision: December 10, 2022
Revised: December 23, 2022
Accepted: February 23, 2023
Article in press: February 23, 2023
Published online: March 15, 2023
ARTICLE HIGHLIGHTS
Research background
Mitophagy plays essential role in the initiation and progression of colorectal cancer (CRC). Mitophagy plays essential role in the initiation and progression of CRC.
Research motivation
The effect of mitophagy-related genes in CRC remains largely unknown.
Research objectives
To develop a mitophagy-related gene signature to predict the survival, immune infiltration and chemotherapy response of CRC patients.
Research methods
Non-negative matrix factorization was used to cluster CRC patients from Gene Expression Omnibus database (GSE39582, GSE17536, and GSE37892) based on mitophagy-related gene expression. The CIBERSORT method was applied for the evaluation of the relative infiltration levels of immune cell types. The performance signature in predicting chemotherapeutic sensitivity was evaluated based on the Genomics of Drug Sensitivity in Cancer database.
Research results
Three clusters with different clinicopathological features and prognosis were identified. Higher enrichment of activated B cells and CD4+ T cells were observed in cluster III patients with the most favorable prognosis. Next, a gene risk model related to mitophagy was produced and patients in training and validation sets were categorized into low-risk and high-risk groups. Low risk patients showed significantly better prognosis, higher enrichment of immune activating cells and greater response to chemotherapy (oxaliplatin, irinotecan and 5-fluorouracil) compared to high risk patients. Further experiments identified CXCL3 as novel regulator of cell proliferation and mitophagy.
Research conclusions
We revealed the biological roles of mitophagy-related genes in the immune infiltration, and its ability to predict patients’ prognosis and response to chemotherapy in CRC. These new findings would offer meaningful insights for the therapeutic management of CRC patients.
Research perspectives
The developed signature in this study will aid in individualizing treatment and follow-up scheme in CRC patients.
