Identification of ferroptosis related genes and subtypes in colorectal cancer
Abstract Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths worldwide. Increasing evidence has shown that ferroptosis plays a significant regulatory role in the occurrence and progression of cancer. However, new biomarkers associated with fe...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-08901-7 |
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| author | Jun Hu Jian Li Yixuan Dong Xin Yue Wenpeng Wang Hongbo Zhang Dalu Kong |
| author_facet | Jun Hu Jian Li Yixuan Dong Xin Yue Wenpeng Wang Hongbo Zhang Dalu Kong |
| author_sort | Jun Hu |
| collection | DOAJ |
| description | Abstract Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths worldwide. Increasing evidence has shown that ferroptosis plays a significant regulatory role in the occurrence and progression of cancer. However, new biomarkers associated with ferroptosis and new ferroptosis-related subtypes in CRC remain to be identified. We collected a colon adenocarcinoma (COAD) dataset from the cancer genome atlas (TCGA) database in UCSC Xena. Ferroptosis-related genes (FRGs) were extracted from the dataset, and we conducted gene expression profiling interactive analysis (GEPIA), cBioPortal analysis, and immune cell infiltration analysis. Additionally, we used the “ConsensusClusterPlus” R package to identify ferroptosis-related subtypes of CRC. Based on these subtypes, we analyzed their prognostic features, gene co-expression networks, and the ferroptosis landscape. We identified 21 FRGs in COAD. The genes RBMS1, NOX4, FABP4, CYB5R1, CPEB1, and ATM were significantly and positively correlated with immune cell infiltration and poor prognosis. Furthermore, we identified two COAD subtypes related to prognosis and ferroptosis (ferroptosis subtype 1 [FS1] and ferroptosis subtype 2 [FS2]). These subtypes were associated with tumor mutation burden (TMB), mutation status, immunogenic cell death (ICD), and immune checkpoint (ICP) regulatory genes. Finally, we established a ferroptosis landscape of COAD. We identified key ferroptosis-related genes and defined two distinct ferroptosis-associated subtypes in CRC that differ significantly in prognosis and immune infiltration. These findings provide new insights into the interaction between ferroptosis and the tumor immune microenvironment, offering potential biomarkers and therapeutic targets for improved diagnosis and personalized treatment of colorectal cancer. |
| format | Article |
| id | doaj-art-7a257a591ec24976b8d2e24175c250f0 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-7a257a591ec24976b8d2e24175c250f02025-08-20T04:01:34ZengNature PortfolioScientific Reports2045-23222025-07-0115111510.1038/s41598-025-08901-7Identification of ferroptosis related genes and subtypes in colorectal cancerJun Hu0Jian Li1Yixuan Dong2Xin Yue3Wenpeng Wang4Hongbo Zhang5Dalu Kong6Department of Colorectal Cancer Surgery, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and HospitalDepartment of Internal Medicine, Tianjin University Hospital, Tianjin UniversityDepartment of Oncology, Tianjin Academy of Traditional Chinese Medicine Affiliated HospitalDepartment of Colorectal Cancer Surgery, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and HospitalDepartment of Colorectal Cancer Surgery, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and HospitalTianjin Marvel Medical Laboratory, Tianjin Marvelbio Technology Co., LtdDepartment of Colorectal Cancer Surgery, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and HospitalAbstract Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths worldwide. Increasing evidence has shown that ferroptosis plays a significant regulatory role in the occurrence and progression of cancer. However, new biomarkers associated with ferroptosis and new ferroptosis-related subtypes in CRC remain to be identified. We collected a colon adenocarcinoma (COAD) dataset from the cancer genome atlas (TCGA) database in UCSC Xena. Ferroptosis-related genes (FRGs) were extracted from the dataset, and we conducted gene expression profiling interactive analysis (GEPIA), cBioPortal analysis, and immune cell infiltration analysis. Additionally, we used the “ConsensusClusterPlus” R package to identify ferroptosis-related subtypes of CRC. Based on these subtypes, we analyzed their prognostic features, gene co-expression networks, and the ferroptosis landscape. We identified 21 FRGs in COAD. The genes RBMS1, NOX4, FABP4, CYB5R1, CPEB1, and ATM were significantly and positively correlated with immune cell infiltration and poor prognosis. Furthermore, we identified two COAD subtypes related to prognosis and ferroptosis (ferroptosis subtype 1 [FS1] and ferroptosis subtype 2 [FS2]). These subtypes were associated with tumor mutation burden (TMB), mutation status, immunogenic cell death (ICD), and immune checkpoint (ICP) regulatory genes. Finally, we established a ferroptosis landscape of COAD. We identified key ferroptosis-related genes and defined two distinct ferroptosis-associated subtypes in CRC that differ significantly in prognosis and immune infiltration. These findings provide new insights into the interaction between ferroptosis and the tumor immune microenvironment, offering potential biomarkers and therapeutic targets for improved diagnosis and personalized treatment of colorectal cancer.https://doi.org/10.1038/s41598-025-08901-7Colorectal cancerFerroptosisConsensus clusterTCGA |
| spellingShingle | Jun Hu Jian Li Yixuan Dong Xin Yue Wenpeng Wang Hongbo Zhang Dalu Kong Identification of ferroptosis related genes and subtypes in colorectal cancer Scientific Reports Colorectal cancer Ferroptosis Consensus cluster TCGA |
| title | Identification of ferroptosis related genes and subtypes in colorectal cancer |
| title_full | Identification of ferroptosis related genes and subtypes in colorectal cancer |
| title_fullStr | Identification of ferroptosis related genes and subtypes in colorectal cancer |
| title_full_unstemmed | Identification of ferroptosis related genes and subtypes in colorectal cancer |
| title_short | Identification of ferroptosis related genes and subtypes in colorectal cancer |
| title_sort | identification of ferroptosis related genes and subtypes in colorectal cancer |
| topic | Colorectal cancer Ferroptosis Consensus cluster TCGA |
| url | https://doi.org/10.1038/s41598-025-08901-7 |
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