MicroRNA Biomarker Discovery For Predicting Platinum Resistance In Ovarian Cancer

Ovarian cancer(OC)is one of the fatal cancers in women.At present,platinum-based drugs are widely used for OC chemotherapy.MicroRNAs(miRNAs)are a class of small non-coding RNAs with 22-24 nucleotides.They hold the potential as biomarkers for disease diagnosis,prognosis and therapy.This study focused on screening miRNA biomarkers for predicting platinum resistance in OC treatment,which had both theoretical and practical significance for the improvement of personalized therapy in OC patients.In methodology,we downloaded gene expression dataset associated with platinum drug based treatment(PDT)of OC from GEO database,and identified differentially expressed genes using Student's t test.Then PDT-associated miRNAs were inferred based on human miRNA-mRNA regulatory network.Finally,PDT-specific miRNA-mRNA network was extracted and the regulatory power of miRNAs was quantified and analyzed,i.e.,number of single-line regulation(NSR)and transcription factor gene percentage(TFP).According to our previous studies,biomarker miRNAs had stronger independent regulatory power and were likely to regulate more TF genes.Hence miRNAs with significantly high NSR and TFP values were screened as candidate biomarkers for predicting platinum resistance in OC treatment.Based on literature searching,clustering analysis,gene ontology and pathway enrichment analyses,the biomarker potential of identified miRNAs was validated and annotated.Moreover,we characterized the functional traits of OC miRNA biomarkers by comparing literature-reported OC prognostic and diagnostic miRNAs,and integrated gene expression data to investigate the homogenous and heterogeneous problems during OC evolution.In summary,a total of 12 miRNAs,miR-579,miR-590-5p,miR-126-3p,miR-182-5p,miR-224-5p,miR-363-3p,miR-448,miR-620,miR-1-3p,mi R-141-3p,let-7g-5p and miR-98-5p,were screened as putative biomarkers for predicting platinum resistance in OC treatment.Among them,seven miRNAs have already been reported as OC biomarkers,and the remaining five could be served as novel biomarkers.Pathway enrichment results showed that the targets of the identified miRNAs were closely involved in OC-related processes,such as TGF-?,p53,Wnt/?-catenin and Cell Cycle signaling.Moreover,miR-448,miR-1-3p,miR-141-3p,let-7g-5p,miR-98-5p,etc.,were found to be associated with OC diagnosis and prognosis,which played crucial roles in OC occurrence and progression.The results convinced the predictive power of the bioinformatics model and further experimental pathogenic analyses were needed in the future work.