Miao YD, Kou ZY, Wang JT, Mi DH. Prognostic implications of ferroptosis-associated gene signature in colon adenocarcinoma. World J Clin Cases 2021; 9(29): 8671-8693 [PMID: 34734046 DOI: 10.12998/wjcc.v9.i29.8671]
Corresponding Author of This Article
Deng-Hai Mi, MD, Chief Doctor, Dean, Professor, Dean’s office, Gansu Academy of Traditional Chinese Medicine, No. 418 Guazhou Road, Qilihe District, Lanzhou 730000, Gansu Province, China. mi.dh@outlook.com
Research Domain of This Article
Oncology
Article-Type of This Article
Clinical and Translational Research
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
World J Clin Cases. Oct 16, 2021; 9(29): 8671-8693 Published online Oct 16, 2021. doi: 10.12998/wjcc.v9.i29.8671
Prognostic implications of ferroptosis-associated gene signature in colon adenocarcinoma
Yan-Dong Miao, Zhi-Yong Kou, Jiang-Tao Wang, Deng-Hai Mi
Yan-Dong Miao, Jiang-Tao Wang, Deng-Hai Mi, The First Clinical Medical College, Lanzhou University, Lanzhou 730000, Gansu Province, China
Zhi-Yong Kou, Department of Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming 650000, Yunnan Province, China
Deng-Hai Mi, Dean’s Office, Gansu Academy of Traditional Chinese Medicine, Lanzhou 730000, Gansu Province, China
Author contributions: Mi DH designed the research; Miao YD and Kou ZY performed the writing, data analysis, and prepared the figures and tables; Wang JT performed the dada validation; Miao YD and Kou ZY contributed equally to this work; All authors approved the final manuscript.
Institutional review board statement: TCGA and GEO belong to public databases. The patients involved in the database have obtained ethical approval. Users can download relevant data for free for research and publish relevant articles. Our study is based on open-source data, so there are no ethical issues and other conflicts of interest. Therefore, the current research was exempt from approval by the local ethics committee. The present study follows the data access strategy and publication guidelines of the TCGA and GEO databases.
Conflict-of-interest statement: All authors declare having no conflict of interests.
Data sharing statement: Bioinformatics analysis code and dataset available from the corresponding author at mi.dh@outlook.com.
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: Deng-Hai Mi, MD, Chief Doctor, Dean, Professor, Dean’s office, Gansu Academy of Traditional Chinese Medicine, No. 418 Guazhou Road, Qilihe District, Lanzhou 730000, Gansu Province, China. mi.dh@outlook.com
Received: March 25, 2021 Peer-review started: March 25, 2021 First decision: June 14, 2021 Revised: June 17, 2021 Accepted: August 19, 2021 Article in press: August 19, 2021 Published online: October 16, 2021 Processing time: 204 Days and 6.9 Hours
ARTICLE HIGHLIGHTS
Research background
Colon adenocarcinoma (COAD) is one of the most common and fatal malignant tumors, which increases the difficulty of prognostic predictions. Ferroptosis is a recently identified programmed cell death process that has the characteristics of iron-dependent lipid peroxide accumulation. However, the predictive value of ferroptosis-related genes (FRGs) for COAD still needs to be further clarified. Therefore, the screening of novel therapeutic targets or prognostic biomarkers based on FRGs could be an essential work for COAD therapy, which could contribute to the improvement of treatment schemes.
Research motivation
This article aims to identify critical FRGs and construct a COAD patient prognostic signature for clinical utilization.
Research objectives
This research addressed the question of the novel FRG gene biomarkers and potential mechanism involved in the development of COAD.
Research methods
The Cancer Genome Atlas database (TCGA) and Gene Expression Omnibus databases were the data sources for mRNA expression and corresponding COAD patient clinical information. Differentially expressed FRGs were recognized using R and Perl software. We constructed a multi-FRG signature of the TCGA-COAD cohort by performing a univariate Cox regression and least absolute shrinkage and selection operator Cox regression analysis. COAD patients from the Gene Expression Omnibus cohort were utilized for verification.
Research results
Most of the FRGs (85%) were differentially expressed between the corresponding adjacent normal tissues and cancer tissues in the TCGA-COAD cohort. Seven FRGs were related to overall survival (OS) in the univariate Cox analysis (all P < 0.05). A model with five FRGs (AKR1C1, AKR1C3, ALOX12, CRYAB, and FDFT1) was constructed to divide patients into high- and low-risk groups. The OS of patients in the high-risk group was significantly lower than that of the low-risk group (all P < 0.01 in the TCGA and Gene Expression Omnibus cohorts). The risk score was an independent prognosticator of OS in the multivariate Cox analysis (hazard ratio > 1, P < 0.01). The predictive capacity of the model was verified by a receiver operating characteristic curve analysis. In addition, a nomogram based on the expression of five hub FRGs and risk score can precisely predict the OS of individual COAD cancer patients. Immune correlation analysis and functional enrichment analysis results revealed that immunology-related pathways were abundant, and the immune states of the high-risk group and the low-risk group were different.
Research conclusions
Our research constructed a new prognostic signature with five FRGs in COAD. The FRG signature proved to be independently related to OS in both the training and validation datasets, thus providing insights into prognostic predictions for COAD. Targeting ferroptosis may be a treatment option for COAD.
Research perspectives
In this study, we identified five FRGs signatures in COAD, and this signature proved to be independently related to OS, suggesting that the five FRG signatures might be novel therapeutic targets for COAD. In our subsequent work, the potential mechanisms between FRGs and tumor immunity in COAD will be investigated, which might contribute to the improvement of treatment schemes.
