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Establishment and validation of a ferroptosis-related signature predicting prognosis and immunotherapy effect in colon cancer
BACKGROUND: Ferroptosis, 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. METHOD: CC transcriptomic and clinical data were downloaded from...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10243598/ https://www.ncbi.nlm.nih.gov/pubmed/37287923 http://dx.doi.org/10.3389/fonc.2023.1201616 |
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author | Li, Zhufeng Yuan, Fang Liu, Xin Wei, Jianming Liu, Tong Li, Weidong Li, Chuan |
author_facet | Li, Zhufeng Yuan, Fang Liu, Xin Wei, Jianming Liu, Tong Li, Weidong Li, Chuan |
author_sort | Li, Zhufeng |
collection | PubMed |
description | BACKGROUND: Ferroptosis, 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. METHOD: CC 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. RESULTS: SLC2A3, 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 (p(merged)<0.001, p(training)<0.001, p(testing)<0.001). TIDE score and IPS were higher in the high-risk group (p(TIDE)<0.005, p(Dysfunction)<0.005, p(Exclusion)<0.001, p(mAb-CTLA-4 )= 3e-08, p(mAb-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). CONCLUSION: This study established a novel prognostic signature and provided more insight into the immunotherapy effect of CC. |
format | Online Article Text |
id | pubmed-10243598 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-102435982023-06-07 Establishment and validation of a ferroptosis-related signature predicting prognosis and immunotherapy effect in colon cancer Li, Zhufeng Yuan, Fang Liu, Xin Wei, Jianming Liu, Tong Li, Weidong Li, Chuan Front Oncol Oncology BACKGROUND: Ferroptosis, 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. METHOD: CC 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. RESULTS: SLC2A3, 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 (p(merged)<0.001, p(training)<0.001, p(testing)<0.001). TIDE score and IPS were higher in the high-risk group (p(TIDE)<0.005, p(Dysfunction)<0.005, p(Exclusion)<0.001, p(mAb-CTLA-4 )= 3e-08, p(mAb-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). CONCLUSION: This study established a novel prognostic signature and provided more insight into the immunotherapy effect of CC. Frontiers Media S.A. 2023-05-23 /pmc/articles/PMC10243598/ /pubmed/37287923 http://dx.doi.org/10.3389/fonc.2023.1201616 Text en Copyright © 2023 Li, Yuan, Liu, Wei, Liu, Li and Li https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Li, Zhufeng Yuan, Fang Liu, Xin Wei, Jianming Liu, Tong Li, Weidong Li, Chuan Establishment and validation of a ferroptosis-related signature predicting prognosis and immunotherapy effect in colon cancer |
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 | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10243598/ https://www.ncbi.nlm.nih.gov/pubmed/37287923 http://dx.doi.org/10.3389/fonc.2023.1201616 |
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