A two-microRNA signature predicts the progression of male thyroid cancer

Abstract

Abstract In various cancers, microRNAs (miRNAs) are abnormally expressed, including thyroid cancer (TC). In recent years, the incidence of TC has increased annually around the world. Compared with female patients, male TC patients are more likely to have a postoperative recurrence and lymph node metastasis, and hence need second treatments. However, the molecular biological processes underlying this phenomenon are not understood. Therefore, we collected data on miRNA expression and clinical information of male TC patients from The Cancer Genome Atlas (TCGA) database. Differentially expressed miRNAs were identified between male TC tissues and matched normal tissues. The Kaplan–Meier method, univariate and multivariate Cox regressions, and receiver operating characteristic curve analyses were performed to assess the association between miRNAs and the disease-free survival of male TC patients. Gene Ontology (GO) and the Kyoto Encyclopaedia of Gene and Genome (KEGG) enrichment analyses were then used to explore the function of miRNA target genes. Furthermore, we evaluated the ability of the miRNA biomarker to predict survival in female TC patients. As a result, a total of 118 differentially expressed miRNAs were identified, including 25 upregulated and 93 downregulated miRNAs. Among them, miR-451a and miR-16-1-3p were confirmed to be independent prognostic factors for the disease-free survival rate. The target genes of miR-451a and miR-16-1-3p were identified, and functional analysis showed that these genes were enriched in 25 Go and KEGG accessions, including cell signal transduction, motor adhesion, phagocytosis, regulation of transcription, cell proliferation, angiogenesis, etc. Neither miR-451a and miR-16-1-3p, nor a prediction model based on both miRNAs effectively predicted survival in female TC patients. In conclusion, both miR-451a and miR-16-1-3p may play important roles in the processes of male TC. The two-miRNA signature involving miR-1258 and miR-193a may serve as a novel prognostic biomarker for male TC patients.