Establishment and validation of a ferroptosis-related signature predicting prognosis and immunotherapy effect in colon cancer

BackgroundFerroptosis, a novel form of regulating cell death, is related to various cancers. However, the role of ferroptosis-related genes (FRGs) on the occurrence and development of colon cancer (CC) needs to be further elucidated.MethodCC transcriptomic and clinical data were downloaded from TCGA...

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Main Authors: Zhufeng Li, Fang Yuan, Xin Liu, Jianming Wei, Tong Liu, Weidong Li, Chuan Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-05-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2023.1201616/full
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author Zhufeng Li
Fang Yuan
Xin Liu
Jianming Wei
Tong Liu
Weidong Li
Chuan Li
author_facet Zhufeng Li
Fang Yuan
Xin Liu
Jianming Wei
Tong Liu
Weidong Li
Chuan Li
author_sort Zhufeng Li
collection DOAJ
description BackgroundFerroptosis, a novel form of regulating cell death, is related to various cancers. However, the role of ferroptosis-related genes (FRGs) on the occurrence and development of colon cancer (CC) needs to be further elucidated.MethodCC transcriptomic and clinical data were downloaded from TCGA and GEO databases. The FRGs were obtained from the FerrDb database. The consensus clustering was performed to identify the best clusters. Then, the entire cohort was randomly divided into the training and testing cohorts. Univariate Cox, LASSO regression and multivariate Cox analyses were used to construct a novel risk model in training cohort. The testing and the merged cohorts were performed to validate the model. Moreover, CIBERSORT algorithm analyze TIME between high- and low- risk groups. The immunotherapy effect was evaluated by analyzing the TIDE score and IPS between high- and low- risk groups. Lastly, RT-qPCR were performed to analyze the expression of the three prognostic genes, and the 2-years OS and DFS between the high- and low- risk groups of 43 clinical CC samples to further validate the value of the risk model.ResultsSLC2A3, CDKN2A, and FABP4 were identified to construct a prognostic signature. Kaplan–Meier survival curves showed that OS between the high- and low-risk groups were statistically significant (pmerged<0.001, ptraining<0.001, ptesting<0.001). TIDE score and IPS were higher in the high-risk group (pTIDE<0.005, pDysfunction<0.005, pExclusion<0.001, pmAb-CTLA-4 = 3e-08, pmAb-PD-1 = 4.1e-10). The clinical samples were divided into high- and low- risk groups according to the risk score. There was a statistical difference in DFS (p=0.0108).ConclusionThis study established a novel prognostic signature and provided more insight into the immunotherapy effect of CC.
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spelling doaj.art-c73e76e7dfa943cf9dbecd2e0c903ec32023-05-23T17:23:28ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-05-011310.3389/fonc.2023.12016161201616Establishment and validation of a ferroptosis-related signature predicting prognosis and immunotherapy effect in colon cancerZhufeng Li0Fang Yuan1Xin Liu2Jianming Wei3Tong Liu4Weidong Li5Chuan Li6Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of General Surgery, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of General Surgery, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of General Surgery, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of General Surgery, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of General Surgery, Tianjin Medical University General Hospital, Tianjin, ChinaBackgroundFerroptosis, a novel form of regulating cell death, is related to various cancers. However, the role of ferroptosis-related genes (FRGs) on the occurrence and development of colon cancer (CC) needs to be further elucidated.MethodCC transcriptomic and clinical data were downloaded from TCGA and GEO databases. The FRGs were obtained from the FerrDb database. The consensus clustering was performed to identify the best clusters. Then, the entire cohort was randomly divided into the training and testing cohorts. Univariate Cox, LASSO regression and multivariate Cox analyses were used to construct a novel risk model in training cohort. The testing and the merged cohorts were performed to validate the model. Moreover, CIBERSORT algorithm analyze TIME between high- and low- risk groups. The immunotherapy effect was evaluated by analyzing the TIDE score and IPS between high- and low- risk groups. Lastly, RT-qPCR were performed to analyze the expression of the three prognostic genes, and the 2-years OS and DFS between the high- and low- risk groups of 43 clinical CC samples to further validate the value of the risk model.ResultsSLC2A3, CDKN2A, and FABP4 were identified to construct a prognostic signature. Kaplan–Meier survival curves showed that OS between the high- and low-risk groups were statistically significant (pmerged<0.001, ptraining<0.001, ptesting<0.001). TIDE score and IPS were higher in the high-risk group (pTIDE<0.005, pDysfunction<0.005, pExclusion<0.001, pmAb-CTLA-4 = 3e-08, pmAb-PD-1 = 4.1e-10). The clinical samples were divided into high- and low- risk groups according to the risk score. There was a statistical difference in DFS (p=0.0108).ConclusionThis study established a novel prognostic signature and provided more insight into the immunotherapy effect of CC.https://www.frontiersin.org/articles/10.3389/fonc.2023.1201616/fullcolon cancerferroptosis-related genesignatureTIMEimmunotherapy
spellingShingle Zhufeng Li
Fang Yuan
Xin Liu
Jianming Wei
Tong Liu
Weidong Li
Chuan Li
Establishment and validation of a ferroptosis-related signature predicting prognosis and immunotherapy effect in colon cancer
Frontiers in Oncology
colon cancer
ferroptosis-related gene
signature
TIME
immunotherapy
title Establishment and validation of a ferroptosis-related signature predicting prognosis and immunotherapy effect in colon cancer
title_full Establishment and validation of a ferroptosis-related signature predicting prognosis and immunotherapy effect in colon cancer
title_fullStr Establishment and validation of a ferroptosis-related signature predicting prognosis and immunotherapy effect in colon cancer
title_full_unstemmed Establishment and validation of a ferroptosis-related signature predicting prognosis and immunotherapy effect in colon cancer
title_short Establishment and validation of a ferroptosis-related signature predicting prognosis and immunotherapy effect in colon cancer
title_sort establishment and validation of a ferroptosis related signature predicting prognosis and immunotherapy effect in colon cancer
topic colon cancer
ferroptosis-related gene
signature
TIME
immunotherapy
url https://www.frontiersin.org/articles/10.3389/fonc.2023.1201616/full
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