Identification of microRNA signatures in thyroid cancer

Abstract

Aim: to identify differentially expressed microRNAs (miRNAs) in papillary and follicular thyroid cancer (TC) and to evaluate their potential as diagnostic and prognostic biomarkers.

Materials and methods. Three GEO datasets were analyzed: GSE104006 (20 samples of papillary TC and 6 normal tissues), GSE191117 (50 samples of papillary TC and 50 normal samples), and GSE62054 (17 samples of follicular carcinoma and 8 benign tumors). Differentially expressed miRNAs were identified with |log2FC| >1 and p < 0.05 with subsequent FDR correction DIANA miRPath v. 3 was used to assess signaling pathways, miRNet v. 2.0 to identify target genes, and ShinyGO v. 0.82 for functional annotation. Prognostic significance was evaluated using ENCORI database.

Results. Six miRNAs were selected: hsa-miR-15a-5p, hsa-miR-146b-5p, hsa-miR-199b-5p, hsa-miR-221-5p, hsa-miR-222-3p, and hsa-miR-484. They potentially regulate over 2,000 target genes, including RET, CCND1, TP53, HIF1A, IL6, and IL1B, which are associated with the development and progression of malignant tumors. GEO analysis revealed their involvement in the regulation of metabolism, biosynthesis, protein modification, as well as in the binding functions of transcription factors, DNA, and RNA. Nineteen KEGG signaling pathways were identified, 13 of which are closely associated with carcinogenesis. Prognostic analysis indicated that low expression of hsa-miR-146b-5p and hsa-miR-221-5p correlate with significantly poorer overall survival in TC patients.

Conclusions. The proposed panel of six miRNAs may have significant potential for the differential diagnosis of papillary and follicular thyroid cancer, risk stratification, and prognosis; hsa-miR-146b-5p and hsa-miR-221-5p demonstrated the greatest prognostic value. Further experimental studies are needed for the clinical validation of these biomarkers.