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

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.

RNA m6A Methylation Regulators Multi-Omics Analysis in Prostate Cancer

“…In addition, the results found that YTHDF1, YTHDF2, and YTHDC2 exhibited a positive correlation, but METTL14, FTO, and ALKBH5 were negatively correlated to Gleason grades (Wu et al, 2021). Some researchers analyzed the important m6A RNA regulators, which act as prognosis factors in prostate cancer, and identified RBMX, NXF1, YTHDF1, HNRNPA2B1, and TRMT112 as critical genes that have great effects on the prognosis of PCa patients (Xu et al, 2020). Many studies have also explored expression patterns and clinical prognostic values of m6A regulators in PCa, which plays a great function in the treatment of PCa (Ou- Yang et al, 2020;Zhang et al, 2021).…”

Identification of N6-Methyladenosine-Associated Long Non-coding RNAs for Immunotherapeutic Response and Prognosis in Patients With Pancreatic Cancer

“…Twenty-five m6A RNA methylation were collected from the m6A2target database 3 ( Deng et al, 2021 ) and literatures ( Tu et al, 2020 ; Xu et al, 2020 ). The expression matrixes of these 25 m6A genes were retrieved from the TCGA, including the expression regulatory factors of writers (METTL3, METTL14, METTL16, CBLL1, ZCCHC4, WTAP, VIRMA, ZC3H13, RBM15, and RBM15B), readers (YTHDC1, YTHDC2, YTHDF1, YTHDF2, YTHDF3, HNRNPC, FMR1, RBMX, HNRNPA2B1, LRRPRC, IGF2BP1, IGF2BP2, and IGF2BP3), and erasers (FTO and ALKBH5).…”

N6-Methylandenosine-Related lncRNA Signature Is a Novel Biomarkers of Prognosis and Immune Response in Colon Adenocarcinoma Patients

“…Both m6A enzymes and lncRNAs are ideal diagnostic and prognostic markers. Accumulating evidence shows that m6Arelated mRNAs and lncRNAs can serve as novel potential targets to predict the prognosis for multiple cancers (Barros-Silva et al, 2020;Li et al, 2020;Meng et al, 2020;Xu et al, 2020Xu et al, , 2021Jin et al, 2021). For instance, METTL14 is a prognosis-associated regulator of m6A RNA methylation in hepatocellular carcinoma (Li et al, 2020).…”