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 to...
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PeerJ Inc.
2021-07-01
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| Online Access: | https://peerj.com/articles/11745.pdf |
| _version_ | 1797418610546704384 |
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| author | Chao Yang Shuoyang Huang Fengyu Cao Yongbin Zheng |
| author_facet | Chao Yang Shuoyang Huang Fengyu Cao Yongbin Zheng |
| author_sort | Chao Yang |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T06:35:23Z |
| format | Article |
| id | doaj.art-a3c6993332af4896adc9a22dbd4e755b |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T06:35:23Z |
| publishDate | 2021-07-01 |
| publisher | PeerJ Inc. |
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| spelling | doaj.art-a3c6993332af4896adc9a22dbd4e755b2023-12-03T10:59:32ZengPeerJ Inc.PeerJ2167-83592021-07-019e1174510.7717/peerj.11745Role of ferroptosis-related genes in prognostic prediction and tumor immune microenvironment in colorectal carcinomaChao Yang0Shuoyang Huang1Fengyu Cao2Yongbin Zheng3Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan, ChinaBackground 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.https://peerj.com/articles/11745.pdfColorectal carcinomaFerroptosisRisk signaturePrognostic predictionTumor immune microenvironment |
| spellingShingle | Chao Yang Shuoyang Huang Fengyu Cao Yongbin Zheng Role of ferroptosis-related genes in prognostic prediction and tumor immune microenvironment in colorectal carcinoma PeerJ Colorectal carcinoma Ferroptosis Risk signature Prognostic prediction Tumor immune microenvironment |
| 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 | Colorectal carcinoma Ferroptosis Risk signature Prognostic prediction Tumor immune microenvironment |
| url | https://peerj.com/articles/11745.pdf |
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