Abstract
BackgroundThe mortality rate of clear cell renal cell carcinoma (ccRCC) remains high. The aim of this study was to identify novel prognostic biomarkers by using m6A RNA methylation regulators capable of improving the risk-stratification criteria of survival for ccRCC patients.MethodsThe gene expression data of 16 m6A methylation regulators and its relevant clinical information were extracted from The Cancer Genome Atlas (TCGA) database. The expression pattern of these m6A methylation regulators were evaluated. Consensus clustering analysis was conducted to identify clusters of ccRCC patients with different prognosis. Univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis were performed to construct multiple-gene risk signature. A survival analysis was carried out to determine the independent prognostic significance of the signature.ResultsFive m6A-related genes (ZC3H13, METTL14, YTHDF2, YTHDF3 and HNRNPA2B1) showed significantly downregulated in tumor tissue, while seven regulators (YTHDC2, FTO, WTAP, METTL3, ALKBH5, RBM15 and KIAA1429) was remarkably upregulated in ccRCC. Consensus clustering analysis identified two clusters of ccRCC with significant differences in overall survival (OS) and tumor stage between them. We also constructed a two-gene signature, METTL3 and METTL14, serving as an independent prognostic indicator for distinguishing ccRCC patients with different prognosis both in training, validation and our own clinical datasets. The receiver operator characteristic (ROC) curve indicated the area under the curve (AUC) in these three datasets were 0.721, 0.684 and 0.828, respectively, demonstrated that the prognostic signature had a good prediction efficiency.Conclusionsm6A methylation regulators exert as potential biomarkers for prognostic stratification of ccRCC patients and may assist clinicians achieving individualized treatment for this patient population.
Highlights
The mortality rate of clear cell renal cell carcinoma remains high
The expression pattern of m 6A RNA methylation regulators in ccRCCIn order to explore the expression pattern of m6A RNA methylation regulators in clear cell renal cell carcinoma (ccRCC), the sequencing data of a total of 16 m 6A related genes were extracted from the The Cancer Genome Atlas (TCGA) ccRCC cohort
The interaction and correlation among the m6A RNA methylation regulators in ccRCCIn order to understand the mutual interaction of the m6A RNA methylation regulators, the PPI network of the chosen 16 genes was constructed based on the String database
Summary
The aim of this study was to identify novel prognostic biomarkers by using m6A RNA methylation regulators capable of improving the risk-stratification criteria of survival for ccRCC patients. RNA modifications have been widely known to play critical roles in the post-transcriptional regulation of gene expression since its discovery in the early 1970s [6]. Accumulative evidence have demonstrated that aberrant expression of those m 6A RNA methylation regulators is associated with multiple diseases such as infertility, obesity, and even cancer [17]. It is clear that m6A methylation regulators play different or even contradictory roles in different types of cancers. Given limited knowledge of the role of m6A methylation in ccRCC, studying the precise correlation between m6A-related regulator gene and its clinical prognosis is in high demand
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
