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 mRNA 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.