The Identification of Critical m6A RNA Methylation Regulators as Malignant Prognosis Factors in Prostate Adenocarcinoma

Jiaju Xu; Yuenan Liu; Jingchong Liu; Tianbo Xu; Gong Cheng; Yi Shou; Junwei Tong; Lilong Liu; Lijie Zhou; Wen Xiao; Zhiyong Xiong; Changfei Yuan; Zhixian Chen; Di Liu; Hongmei Yang; Huageng Liang; Ke Chen; Xiaoping Zhang

doi:10.3389/fgene.2020.602485

The Identification of Critical m⁶A RNA Methylation Regulators as Malignant Prognosis Factors in Prostate Adenocarcinoma

Front Genet. 2020 Dec 4:11:602485. doi: 10.3389/fgene.2020.602485. eCollection 2020.

Authors

Jiaju Xu¹, Yuenan Liu¹, Jingchong Liu¹, Tianbo Xu¹, Gong Cheng¹, Yi Shou¹, Junwei Tong¹, Lilong Liu¹, Lijie Zhou¹, Wen Xiao¹, Zhiyong Xiong¹, Changfei Yuan¹, Zhixian Chen¹, Di Liu¹, Hongmei Yang², Huageng Liang¹, Ke Chen¹, Xiaoping Zhang¹

Affiliations

¹ Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Department of Pathogenic Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.

Abstract

RNA methylation accounts for over 60% of all RNA modifications, and N⁶-methyladenosine (m⁶A) is the most common modification on mRNA and lncRNA of human beings. It has been found that m⁶A modification occurs in microRNA, circRNA, rRNA, and tRNA, etc. The m⁶A modification plays an important role in regulating gene expression, and the abnormality of its regulatory mechanism refers to many human diseases, including cancers. Pitifully, as it stands there is a serious lack of knowledge of the extent to which the expression and function of m⁶A RNA methylation can influence prostate cancer (PC). Herein, we systematically analyzed the expression levels of 35 m⁶A RNA methylation regulators mentioned in literatures among prostate adenocarcinoma patients in the Cancer Genome Atlas (TCGA), finding that most of them expressed differently between cancer tissues and normal tissues with the significance of p < 0.05. Utilizing consensus clustering, we divided PC patients into two subgroups based on the differentially expressed m⁶A RNA methylation regulators with significantly different clinical outcomes. To appraise the discrepancy in total transcriptome between subgroups, the functional enrichment analysis was conducted for differential signaling pathways and cellular processes. Next, we selected five critical genes by the criteria that the regulators had a significant impact on prognosis of PC patients from TCGA through the last absolute shrinkage and selection operator (LASSO) Cox regression and obtained a risk score by weighted summation for prognosis prediction. The survival analysis curve and receiver operating characteristic (ROC) curve showed that this signature could excellently predict the prognosis of PC patients. The univariate and multivariate Cox regression analyses proved the independent prognostic value of the signature. In summary, our effort revealed the significance of m⁶A RNA methylation regulators in prostate cancer and determined a m⁶A gene expression classifier that well predicted the prognosis of prostate cancer.

Keywords: LASSO Cox regression; Ncpsdummy6-methyladenosine; RNA methylation; biomarker; consensus clustering; methyltransferase; prognostic signature; prostate adenocarcinoma.