Cross-talk and clinical value of m[superscript 6]A regulatory gene in bladder cancer

RNA modification is a regulation at the post-transcriptional level. RNA methylation modification accounts for more than 60% of all RNA modifications, and m[superscript 6]A(6-methyladenine) is the most common type of RNA methylation modification on mRNA of higher organisms. The modification level of transcription m[superscript 6]A is dynamically regulated by methyltransferase (reader), binding protein (writer) and demethylase (eraser). Furthermore, m[superscript 6]A methylation has been found to have an impact on tumor initiation and progression through various mechanisms.

13 genes related m[superscript 6]A from all the gene expressions in The Cancer Genome Atlas (TCGA) were screened. Gene Ontology (GO) and KEGG analysis were applied to explore the functions of genes identified in study. We clustered the related regulators of m[superscript 6]A into three subgroups with "ConsensusClusterPlus". 13 genes were used for univariate Cox analysis to find genes associated with prognosis, and the risk model was constructed based on lasso regression. According to the median risk score of each patient, the patients were divided into high and low risk groups for survival analysis. The ROC curve evaluates the model. Then the risk group and clinical characteristics were analyzed.

The three subgroups had different clinical characteristics. Our tumor clusters were related to grade, survival status. Moreover, we observed a significantly longer overall survival (OS) in the cluster 1 than the cluster 2 and cluster 3. Three m[superscript 6]A-related genes related to prognosis were used to construct a prognostic risk model. We found age are independent prognostic marker. What's more, risk score can also be an independent prognostic factor.

Revealing the regulation and functional mechanism of cross-talk among m[superscript 6]A writers, erasers, and readers, and determine its role in bladder cancer may help in developing novel and efficient strategies for the diagnosis, prognosis and treatment of bladder cancer.