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Role of ferroptosis-related genes in prognostic prediction and tumor immune microenvironment in colorectal carcinoma

BACKGROUND AND AIM: Colorectal cancer (CRC) ranks the second most common cause of cancer-related mortality worldwide. Ferroptosis, a recently discovered form of programmed cell death different from other, raises promising novel opportunities for therapeutic intervention of CRC. This study intended t...

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Autores principales: Yang, Chao, Huang, Shuoyang, Cao, Fengyu, Zheng, Yongbin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286063/
https://www.ncbi.nlm.nih.gov/pubmed/34316400
http://dx.doi.org/10.7717/peerj.11745
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author Yang, Chao
Huang, Shuoyang
Cao, Fengyu
Zheng, Yongbin
author_facet Yang, Chao
Huang, Shuoyang
Cao, Fengyu
Zheng, Yongbin
author_sort Yang, Chao
collection PubMed
description BACKGROUND AND AIM: Colorectal cancer (CRC) ranks the second most common cause of cancer-related mortality worldwide. Ferroptosis, a recently discovered form of programmed cell death different from other, raises promising novel opportunities for therapeutic intervention of CRC. This study intended to systematically assess the prognosis value and multiple roles of the ferroptosis-related genes in the tumor immune microenvironment of CRC. MATERIALS AND METHODS: Of 1,192 CRC patients with complete information from the public datasets (TCGA CRC, GEO GSE39582 and GSE17538 cohorts) were selected for analysis. Firstly, K-means consensus clustering was performed to identify ferroptosis-associated subtypes in CRC patients. Subsequently, we constructed a risk signature based on ferroptosis-related genes in TCGA cohort and acquired its validation in two GEO cohorts. Additionally, we established a nomogram integrating the risk signature and clinical factors to improve risk assessment of CRC patients. RESULTS: Five molecular subtypes were identified by consensus clustering for ferroptosis-related genes. There were significant differences in the overall survival, immune cells infiltration status and PD1/PD-L1 mRNA among the five clusters. Then, a risk signature based on the ten-gene was constructed which could distinguish effectively high-risk group among CRC patients in both training and validation sets. The high-risk patients were more likely to have an inhibitory immune microenvironment and lower stemness features. A prognostic nomogram integrated risk signature and clinicopathological features could be used as a more accurate prognostic prediction visualization tool than TNM stage alone. CONCLUSION: This ferroptosis risk signature may accurately differentiate between different risk populations and predict the prognosis of CRC. Besides, this study elucidated the crucial role of ferroptosis in tumor immune microenvironment.
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spelling pubmed-82860632021-07-26 Role of ferroptosis-related genes in prognostic prediction and tumor immune microenvironment in colorectal carcinoma Yang, Chao Huang, Shuoyang Cao, Fengyu Zheng, Yongbin PeerJ Bioinformatics BACKGROUND AND AIM: Colorectal cancer (CRC) ranks the second most common cause of cancer-related mortality worldwide. Ferroptosis, a recently discovered form of programmed cell death different from other, raises promising novel opportunities for therapeutic intervention of CRC. This study intended to systematically assess the prognosis value and multiple roles of the ferroptosis-related genes in the tumor immune microenvironment of CRC. MATERIALS AND METHODS: Of 1,192 CRC patients with complete information from the public datasets (TCGA CRC, GEO GSE39582 and GSE17538 cohorts) were selected for analysis. Firstly, K-means consensus clustering was performed to identify ferroptosis-associated subtypes in CRC patients. Subsequently, we constructed a risk signature based on ferroptosis-related genes in TCGA cohort and acquired its validation in two GEO cohorts. Additionally, we established a nomogram integrating the risk signature and clinical factors to improve risk assessment of CRC patients. RESULTS: Five molecular subtypes were identified by consensus clustering for ferroptosis-related genes. There were significant differences in the overall survival, immune cells infiltration status and PD1/PD-L1 mRNA among the five clusters. Then, a risk signature based on the ten-gene was constructed which could distinguish effectively high-risk group among CRC patients in both training and validation sets. The high-risk patients were more likely to have an inhibitory immune microenvironment and lower stemness features. A prognostic nomogram integrated risk signature and clinicopathological features could be used as a more accurate prognostic prediction visualization tool than TNM stage alone. CONCLUSION: This ferroptosis risk signature may accurately differentiate between different risk populations and predict the prognosis of CRC. Besides, this study elucidated the crucial role of ferroptosis in tumor immune microenvironment. PeerJ Inc. 2021-07-14 /pmc/articles/PMC8286063/ /pubmed/34316400 http://dx.doi.org/10.7717/peerj.11745 Text en ©2021 Yang et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Bioinformatics
Yang, Chao
Huang, Shuoyang
Cao, Fengyu
Zheng, Yongbin
Role of ferroptosis-related genes in prognostic prediction and tumor immune microenvironment in colorectal carcinoma
title Role of ferroptosis-related genes in prognostic prediction and tumor immune microenvironment in colorectal carcinoma
title_full Role of ferroptosis-related genes in prognostic prediction and tumor immune microenvironment in colorectal carcinoma
title_fullStr Role of ferroptosis-related genes in prognostic prediction and tumor immune microenvironment in colorectal carcinoma
title_full_unstemmed Role of ferroptosis-related genes in prognostic prediction and tumor immune microenvironment in colorectal carcinoma
title_short Role of ferroptosis-related genes in prognostic prediction and tumor immune microenvironment in colorectal carcinoma
title_sort role of ferroptosis-related genes in prognostic prediction and tumor immune microenvironment in colorectal carcinoma
topic Bioinformatics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286063/
https://www.ncbi.nlm.nih.gov/pubmed/34316400
http://dx.doi.org/10.7717/peerj.11745
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