Appraising microRNA-99a as a novel prognostic biomarker across 21 human cancer types based on data from the cancer genome atlas

Background: MicroRNA-99a has been believed to play a critical role in progression in various cancers; however, the prognostic and clinicopathological value of microRNA-99a in cancers remains unclarified. Methods and Results: We first evaluated the prognostic significance of microRNA-99a expression in 21 human cancer types in The Cancer Genome Atlas (TCGA). Patients with lower microRNA-99a levels had lower chances of overall survival in lung adenocarcinoma, esophageal cancer, cervical cancer, and head and neck squamous cell carcinoma, whereas they were more likely to survive urothelial bladder cancer and cutaneous melanoma. Subsequently, we included seven studies with sufficient data to further assesse microRNA-99a expression and its prognostic significance in human cancer types using meta-analysis. Low microRNA-99a level was closely linked with poor survival according to the published studies (HR=2.531, 95% CI: 1.920~3.337), but not in TCGA data (HR=1.042, 95% CI: 0.971-1.119). It clearly showed that down regulation of microRNA-99a was closely associated with shorter survival according to published studies and TCGA data (HR=1.101, 95% CIs 1.028~1.179). Finally, the bioinformatics analysis revealed that microRNA-99a might be involved in complex cellular pathways by Gene Ontology (GO) Biological Processes term, such as regulation of transcription. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that glycosaminoglycan biosynthesis and mitogen-activated protein kinase (MAPK) pathway were the most significant pathways regulated by microRNA-99a. The Search Tool for the Retrieval of Interacting Genes/ Proteins (STRING) also visualized the protein interaction and the related pathways in this study. Conclusions: These results indicate that microRNA-99a may be a reliable indicator for the progression and outcome in cancers patients.