Relationship between m6A RNA methylation regulators and prognosis of prostate cancer / 中国医科大学学报

ABSTRACT

Objective To explore the relationship between m6A RNA methylation regulators and prognosis of prostate cancer.Methods Clinicopathological and mRNA-related data of 496 cases of prostate cancer were downloaded from the Cancer Genome Atlas(TCGA)database,and 12 m6A regulators were identified:METTL3,METTL14,WTAP,RBM15,ZC3H13,YTHDC1,YTHDC2,YTHDF1,YTHDF2,HNRNPC,FTO,and ALKBH5.The m6A regulators differentially expressed in prostate cancer samples were screened.Unsupervised clustering of prostate cancer tissues was used to compare differences in overall survival.Multivariate Cox regres-sion analysis was used to divide patients into high-and low-risk groups according to the risk scores,and survival rates were compared.The risk score of clinicopathological factors was determined,and a multivariate Cox regression analysis model was constructed to evaluate the prognostic prediction value.Immunohistochemical staining was performed to detect METTL14 and FTO expression in prostate cancer tis-sues.Results Eight differentially expressed regulators were screened from 12 m6A regulators.Unsupervised cluster analysis divided the samples into Clusters 1,2,and 3 and found significant differences in survival time in all three groups.Multivariate Cox regression analyses revealed that METTL14and FTOwere strongly associated with the prognosis of patients with prostate cancer.A Cox regression model con-structed to score the risk of prostate cancer revealed that the high-and low-risk groups had survival differences,and the risk score could be used as an independent prognostic factor.The positive expression rates of METTL14 and FTO protein in prostate cancer tissues were significantly higher than those in adjacent tissues(P<0.05).Conclusion In this study,a prognostic prediction model based on m6A regulators of prostate cancer was constructed,in which the risk score could be used as an independent prognostic factor.METTL14and FTOcould be used as molecular markers for the diagnosis of prostate cancer and as potential targets for treatment.