Prognostic and Clinical Significance of miRNA-205 in Endometrioid Endometrial Cancer

Abstract

Endometrial cancer is one of the most common malignancies of the reproductive female tract, with endometrioid endometrial cancer being the most frequent type. Despite the relatively favourable prognosis in cases of endometrial cancer, there is a necessity to evaluate clinical and prognostic utility of new molecular markers. MiRNAs are small, non-coding RNA molecules that take part in RNA silencing and post-transcriptional regulation of gene expression. Altered expression of miRNAs may be associated with cancer initiation, progression and metastatic capabilities. MiRNA-205 seems to be one of the key regulators of gene expression in endometrial cancer. In this study, we investigated clinical and prognostic role of miRNA-205 in endometrioid endometrial cancer. After total RNA extraction from 100 archival formalin-fixed paraffin-embedded tissues, real-time quantitative RT-PCR was used to define miRNA-205 expression levels. The aim of the study was to evaluate miRNA-205 expression levels in regard to patients' clinical and histopathological features, such as: survival rate, recurrence rate, staging, myometrial invasion, grading and lymph nodes involvement. Higher levels of miRNA-205 expression were observed in tumours with less than half of myometrial invasion and non-advanced cancers. Kaplan-Maier analysis revealed that higher levels of miRNA-205 were associated with better overall survival (p = 0,034). These results indicate potential clinical utility of miRNA-205 as a prognostic marker.

Fig 1

Laser microdissection technique–general overview showing basic steps, according to MMI CellCut system protocol (A–selection of paraffin embedded tissue blocks and sectioning of blocks; B–placing sections on membrane-slides which are protected by glass slides; C–selection of tissue and cutting with laser: 1 –UV laser, 2 –focusing lenses, 3- polarization beam combiner, 4 –objective, 5 –membrane-slide with tissue section; D–final product, microdissected tissues may be collected by an adhesive cap).

Fig 2. MiRNA-205 expression in normal and endometrioid endometrial cancer tissue samples (Mann Whitney U test, p = 0,000158).

Fig 3. MiRNA-205 expression: I, II vs. III, IV FIGO stage (p = 0,045).

Fig 4. MiRNA-205 expression in terms of grading: G1 vs. G2 vs. G3 (Kruskal–Wallis test, G2 vs. G3, p = 0.02).

Fig 5. MiRNA-205 expression: < ½ myometrial invasion vs. ≥ ½ myometrial invasion (Mann-Whitney U test, p = 0,03).

Fig 6. Kaplan-Meier survival analysis based on miRNA-205 expression values (cut-off expression value ΔΔCt = 0.4).

High expression of miRNA-205 vs. low expression of miRNA-205 (HR 0,34, 95% CI 0.21–0.82; log-rank test, p = 0,034).