Comprehensive analysis of miRNA-gene regulatory network with clinical significance in human cancers

microRNAs(miRNAs),particularly the exosomal miRNAs have been widely used as biomarkers and promising therapeutic targets in cancer.However,a comprehensive analysis of miRNA-gene regulatory network with clinical significance remains scarce.The emergence of high-throughput multi-omics data over large,well-characterized patient cohorts provides an unprecedented opportunity to address this problem.Herein,we performed a clinic-centered analysis to identify cancer-associated miRNAs,miRNA-target axis.We first calculated the correlation among miRNA,mRNA and 75 unique clinico-pathological characteristics(CPCs)in 26 cancer types,and established an online resource(4CR).Interestingly,we found that the high expression of several DNA methylation-related enzymes was associated with adverse outcomes of cancer patients,and these genes were regulated by a cluster of miRNAs.Furthermore,by integrating exosomal miRNA and m RNA databases,we identified exosomal miRNA biomarkers for non-invasive cancer surveillance and therapy monitoring.Finally,we explored the role of CPC-related miRNAs for therapeutic effect prediction of drugs based on their shared targets.Our analysis pipeline illustrated the significance of clinic-centered analysis in miRNA-gene pair identification and provided helpful clues for future cancer studies.