ABSTRACT: The aim of the presented study was to define tissue and plasma miRNA signatures, which could potentially serve as diagnostic and prognostic markers in endometrioid endometrial cancer (EEC), and to investigate miRNA profiles in regard to clinicopathological characteristics of the tumors. Results: qPCR validation revealed regulation of 14 miRNAs in EEC tissues (miR-9, miR-141,miR-205,miR-203,miR-183,miR-200a*,miR-200b*,miR-200a,miR-200c,miR-429,miR-200b,miR-410,miR-92a,miR-1305) and 9 in plasma samples (miR-449a,miR-1290,miR-1228,miR-203,miR-200a,miR-141,miR-92a, miR-9, miR-301b). Expression of certain miRNAs showed association with FIGO stage, grade and relapse. Two miRNA signatures, miR-205/miR-410 and miR-410/miR-429/miR-92a, classified tumor tissues with higher accuracy in comparison to single miRNAs (AUC 0.972, 95% CI 0.919-0.995 and 0.991, 95% CI 0.948-1.000, resepctively). miRNA signature composed of miR-205 and miR-200a predicted relapse with AUC of 0.854 (95% CI 0.691-0.951). Tissue miRNA signatures were independent prognostic markers of overall (miR-1228/miR-200c/miR-429, HR 2.98) and progression-free survival (miR-1228/miR-429, HR 4.149). Plasma miRNA signatures classified EEC plasma samples with high accuracy. Conclusions: We conclude that miRNA signatures hold great promise for becoming non-invasive biomarkers for early EEC detection and prognosis. Tissue samples were collected from 122 women (77 EEC and 45 controls). Expression profiling of 866 human miRNAs and 89 human viral miRNAs was performed in 24 samples and was followed by qPCR validation in 104 patients. Of 24 samples analyzed by microarrays, 22 (18 EEC, 4 normal controls) were available for final analysis. Expression of 14 miRNAs was analysed in 48 plasma samples by qPCR.
