The prognostic role of miR-181a-5p in advanced stages epithelial ovarian cancer patients enrolled in MITO16A/MaNGO-OV2 clinical trial

Background: Previous data from mono-institutional small studies suggested that tumor expression of miR-181a-5p and levels of phospho-Smad2 (P-Smad2) correlated with poor prognosis in advanced ovarian cancer patients. This study aimed to validate these findings in a large, multicentric cohort enrolled in a phase IV clinical trial (Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO-16A)/Mario Negri Gynecologic Oncology group (MaNGO-OV2)). Methods: Out of 398 advanced-stage epithelial ovarian cancer patients, mostly (>80%) classified as high-grade serous histotype, undergoing cytoreductive surgery followed by carboplatin, paclitaxel and bevacizumab treatment, miR-181a-5p levels were examined in 271 cases (quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR)), and P-Smad2 levels in 324 cases (immunohistochemistry); both techniques were applied to 253 patients. Results: Setting a best-cut off value of 2.4. We subdivided patients in those with high (n = 256) and low (n = 15) miR-181a-5p expression levels. In multivariate analysis miR-181a-5p was found to be an independent prognostic biomarker associated with Progression-Free Survival (PFS)(high vs. low Hazard Ratio (HR) = 5.25; 95% Confidence Interval (CI) = 1.32–20.80, p = 0.018). No association was found between miR-181a-5p expression and the Overall Survival (OS) (high vs. low HR = 2.25; 95% CI = 0.60–8.52, p = 0.232). P-Smad2 levels appeared to be related to prognosis, but stringent statistical analysis did not demonstrate a significant association with PFS (p = 0.625) or OS (p = 0.205). Conclusions: Results confirm the prognostic role of miR-181a-5p. Increased miR-181a-5p expression is associated with short PFS, suggesting its potential as a prognostic biomarker for advanced ovarian cancer patients treated with carboplatin, paclitaxel and bevacizumab. Clinical Trial Registration: NCT01706120.

Ovarian cancer; Clinical trial; Prognostic biomarker; miR-181a-5p

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