Identification of endometrioid endometrial carcinoma-associated microRNAs in tissue and plasma. Homo sapiens

A set of endometrioid endometrial carcinoma (EEC)-associated miRNAs in tissue and plasma were identified by next-generation sequencing approach, which could enable in-depth characterization of the global repertoire of miRNAs. First, by next-generation sequencing analysis, 11 candidate EEC-associated miRNAs (hsa-miR-10b, hsa-miR-499, hsa-miR-184, hsa-miR-195, hsa-miR-135b, hsa-miR-203, hsa-miR-10a, hsa-miR-30a-5p, hsa-miR-205, hsa-miR-30a-3p, hsa-miR-21) were identified. Subsequently, by confirmation analysis of qRT-PCR, eight EEC-associated miRNAs (up-regulated: has-miR-499, has-miR-135b, hsa-miR-205, down-regulated: hsa-miR-10b, hsa-miR-195, hsa-miR-30a-5p, hsa-miR-30a-3p and hsa-miR-21) in tissue were identified. The expression level of has-miR-499 in FIGO stage II or more advanced tumors was significantly higher than that in FIGO stages I tumors. The expression level of has-miR-205 in EEC Grade 3 was significantly higher than that in EEC Grades 1 and 2. The expression level of has-miR-499 in FIGO stage IA and Grade 1 tissues was significantly lower than that in others (stage FIGO IB or more advanced, and Grade 2 or 3). By receiver operating characteristic (ROC) curves analysis, in comparison to single EEC-associated miRNA, two miRNAs signatures (miR135b/miR195 and miR135b/miR30a-3p) could distinguish between EEC and normal endometrial (NE) tissue samples yielding high area under curves (AUC) of 0.9835 (95%CI: 0.9677-1.000, p<0.048, Wald test), and 0.9898 (95%CI: 0.9677-1.000, p<0.038, Wald test), respectively. As possible non-invasive marker for EEC, four EEC-associated miRNAs (increased level: hsa-miR-135b, hsa-miR-205, decreased-level: hsa-miR-30a-3p and hsa-miR-21) in plasma were identified. Circulating levels of three EEC-associated miRNAs (hsa-miR-135b, hsa-miR-205 and hsa-miR-30a-3p) in plasma were significantly decreased after hysterectomy. Plasma concentration of miR-21 in cases of FIGO stage IA and Grade 1 tumors were significantly higher than that in cases of more advanced tumors. ROC curves analysis revealed that miR-135b and miR-205 levels in plasma yielded AUCs of 0.9722 (95%CI: 0.913-1.000) and 1.00 (95%CI: 1.000-1.000), respectively. The measurement of EEC-associated miRNAs in tissue and plasma may be used as early detection, diagnostic, prognostic, and follow-up test for EEC.