TY - JOUR
T1 - N6-methylandenosine-related gene expression signatures for predicting the overall survival and immune responses of patients with colorectal cancer
AU - Yu, Lili
AU - Wang, Lijuan
AU - Sun, Jing
AU - Zhou, Xuan
AU - Hu, Yeting
AU - Hu, Lidan
AU - He, Yazhou
AU - Lin, Chunqing
AU - Chen, Jie
AU - Xu, Xiaolin
AU - Dunlop, Malcolm G
AU - Theodoratou, Evropi
AU - Ding, Kefeng
AU - Li, Xue
N1 - Funding Information:
XL is supported by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001) and the National Nature Science Foundation of China (82204019). KD is supported by the Project of the regional diagnosis and treatment center of the Health Planning Committee (No. JBZX-201903). ET is supported by a CRUK Career Development Fellowship (C31250/A22804). This work is also funded by a grant to MGD as Project Leader with the MRC Human Genetics Unit Centre Grant (U127527198).
Publisher Copyright:
Copyright © 2023 Yu, Wang, Sun, Zhou, Hu, Hu, He, Lin, Chen, Xu, Dunlop, Theodoratou, Ding and Li.
PY - 2023/3/3
Y1 - 2023/3/3
N2 - 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.
AB - 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.
U2 - 10.3389/fgene.2023.885930
DO - 10.3389/fgene.2023.885930
M3 - Article
C2 - 36936424
VL - 14
SP - 885930
JO - Frontiers in genetics
JF - Frontiers in genetics
SN - 1664-8021
ER -