N6-methyladenosine related gene expression signatures for predicting the overall survival and immune responses of patients with colorectal cancer
N6-methyladenosine (m6A) modification has been demonstrated to exhibit a crucial prognostic effect on colorectal cancer (CRC). Nonetheless, potential mechanism of m6A in survival rate and immunotherapeutic response remains unknown. Here we investigated the genes associated with m6A regulators and de...
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| Format: | Article |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.885930/full |
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| author | Lili Yu Lili Yu Lijuan Wang Jing Sun Xuan Zhou Yeting Hu Lidan Hu Yazhou He Chunqing Lin Jie Chen Xiaolin Xu Malcolm G. Dunlop Evropi Theodoratou Evropi Theodoratou Kefeng Ding Kefeng Ding Xue Li |
| author_facet | Lili Yu Lili Yu Lijuan Wang Jing Sun Xuan Zhou Yeting Hu Lidan Hu Yazhou He Chunqing Lin Jie Chen Xiaolin Xu Malcolm G. Dunlop Evropi Theodoratou Evropi Theodoratou Kefeng Ding Kefeng Ding Xue Li |
| author_sort | Lili Yu |
| collection | DOAJ |
| description | N6-methyladenosine (m6A) modification has been demonstrated to exhibit a crucial prognostic effect on colorectal cancer (CRC). Nonetheless, potential mechanism of m6A in survival rate and immunotherapeutic response remains unknown. Here we investigated the genes associated with m6A regulators and developed a risk score for predicting the overall survival (OS) of CRC patients. RNA-seq transcriptomic profiling data of COAD/READ samples were obtained from The Cancer Genome Atlas (TCGA) database. Absolute Shrinkage and Selection Operator (LASSO)- Cox regression analysis was conducted to identify the m6A-related gene expression signatures and the selected genes were inputted into stepwise regression to develop a prognostic risk score in TCGA, and its predictive performance of CRC survival was further validated in Gene Expression Omnibus (GEO) datasets. According to our results, the risk score comprising 18 m6A-related mRNAs was significantly associated with CRC survival in both TCGA and GEO datasets. And the stratified analysis also confirmed that high-risk score acted as a poor factor in different age, sex, T stage, and tumour, node, metastasis (TNM) stages. The m6A-related prognostic score in combination with clinical characteristics yielded time-dependent area under the receiver operating characteristic curve (AUCs) of 0.85 (95%CI: 0.79–0.91), 0.84 (95%CI: 0.79–0.90) and 0.80 (95%CI: 0.71–0.88) for the prediction of the 1-, 3-, 5-year OS of CRC in TCGA cohort. Furthermore, mutation of oncogenes occurred more frequently in the high-risk group and the composition of immune cells in tumour microenvironment (TME) was significantly distinct between the low- and high-risk groups. The low-risk group had a lower microsatellite instability (MSI) score, T-cell exclusion score and dysfunction score, implying that low-risk patients may have a better immunotherapy response than high-risk patients. In summary, a prognostic risk score derived from m6A-related gene expression signatures could serve as a potential prognostic predictor for CRC survival and indicator for predicting immunotherapy response in CRC patients. |
| first_indexed | 2024-04-10T06:03:18Z |
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| id | doaj.art-ecf63638bb2340729e152e54f2c2b13f |
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| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-10T06:03:18Z |
| publishDate | 2023-03-01 |
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| spelling | doaj.art-ecf63638bb2340729e152e54f2c2b13f2023-03-03T05:58:40ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-03-011410.3389/fgene.2023.885930885930N6-methyladenosine related gene expression signatures for predicting the overall survival and immune responses of patients with colorectal cancerLili Yu0Lili Yu1Lijuan Wang2Jing Sun3Xuan Zhou4Yeting Hu5Lidan Hu6Yazhou He7Chunqing Lin8Jie Chen9Xiaolin Xu10Malcolm G. Dunlop11Evropi Theodoratou12Evropi Theodoratou13Kefeng Ding14Kefeng Ding15Xue Li16Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaAnalytics of The Second Affiliated Hospital and Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data, Zhejiang University School of Medicine, Hangzhou, ChinaAnalytics of The Second Affiliated Hospital and Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data, Zhejiang University School of Medicine, Hangzhou, ChinaAnalytics of The Second Affiliated Hospital and Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data, Zhejiang University School of Medicine, Hangzhou, ChinaAnalytics of The Second Affiliated Hospital and Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaThe Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, ChinaDepartment of Oncology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, ChinaNational Cancer Center, National Clinical Research Center for Cancer, and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaCenter for Global Health, Zhejiang University, Hangzhou, ChinaAnalytics of The Second Affiliated Hospital and Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data, Zhejiang University School of Medicine, Hangzhou, ChinaCancer Research UK Edinburgh Centre, Medical Research Council Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United KingdomCancer Research UK Edinburgh Centre, Medical Research Council Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United KingdomCentre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, United KingdomDepartment of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaCancer Center, Zhejiang University, Hangzhou, ChinaAnalytics of The Second Affiliated Hospital and Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data, Zhejiang University School of Medicine, Hangzhou, ChinaN6-methyladenosine (m6A) modification has been demonstrated to exhibit a crucial prognostic effect on colorectal cancer (CRC). Nonetheless, potential mechanism of m6A in survival rate and immunotherapeutic response remains unknown. Here we investigated the genes associated with m6A regulators and developed a risk score for predicting the overall survival (OS) of CRC patients. RNA-seq transcriptomic profiling data of COAD/READ samples were obtained from The Cancer Genome Atlas (TCGA) database. Absolute Shrinkage and Selection Operator (LASSO)- Cox regression analysis was conducted to identify the m6A-related gene expression signatures and the selected genes were inputted into stepwise regression to develop a prognostic risk score in TCGA, and its predictive performance of CRC survival was further validated in Gene Expression Omnibus (GEO) datasets. According to our results, the risk score comprising 18 m6A-related mRNAs was significantly associated with CRC survival in both TCGA and GEO datasets. And the stratified analysis also confirmed that high-risk score acted as a poor factor in different age, sex, T stage, and tumour, node, metastasis (TNM) stages. The m6A-related prognostic score in combination with clinical characteristics yielded time-dependent area under the receiver operating characteristic curve (AUCs) of 0.85 (95%CI: 0.79–0.91), 0.84 (95%CI: 0.79–0.90) and 0.80 (95%CI: 0.71–0.88) for the prediction of the 1-, 3-, 5-year OS of CRC in TCGA cohort. Furthermore, mutation of oncogenes occurred more frequently in the high-risk group and the composition of immune cells in tumour microenvironment (TME) was significantly distinct between the low- and high-risk groups. The low-risk group had a lower microsatellite instability (MSI) score, T-cell exclusion score and dysfunction score, implying that low-risk patients may have a better immunotherapy response than high-risk patients. In summary, a prognostic risk score derived from m6A-related gene expression signatures could serve as a potential prognostic predictor for CRC survival and indicator for predicting immunotherapy response in CRC patients.https://www.frontiersin.org/articles/10.3389/fgene.2023.885930/fullcolorectal cancerprognostic risk scoregene expressionoverall survivalimmune responses |
| spellingShingle | Lili Yu Lili Yu Lijuan Wang Jing Sun Xuan Zhou Yeting Hu Lidan Hu Yazhou He Chunqing Lin Jie Chen Xiaolin Xu Malcolm G. Dunlop Evropi Theodoratou Evropi Theodoratou Kefeng Ding Kefeng Ding Xue Li N6-methyladenosine related gene expression signatures for predicting the overall survival and immune responses of patients with colorectal cancer Frontiers in Genetics colorectal cancer prognostic risk score gene expression overall survival immune responses |
| title | N6-methyladenosine related gene expression signatures for predicting the overall survival and immune responses of patients with colorectal cancer |
| title_full | N6-methyladenosine related gene expression signatures for predicting the overall survival and immune responses of patients with colorectal cancer |
| title_fullStr | N6-methyladenosine related gene expression signatures for predicting the overall survival and immune responses of patients with colorectal cancer |
| title_full_unstemmed | N6-methyladenosine related gene expression signatures for predicting the overall survival and immune responses of patients with colorectal cancer |
| title_short | N6-methyladenosine related gene expression signatures for predicting the overall survival and immune responses of patients with colorectal cancer |
| title_sort | n6 methyladenosine related gene expression signatures for predicting the overall survival and immune responses of patients with colorectal cancer |
| topic | colorectal cancer prognostic risk score gene expression overall survival immune responses |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.885930/full |
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