Synergy of the microRNA Ratio as a Promising Diagnosis Biomarker for Mucinous Borderline and Malignant Ovarian Tumors

Enora Dolivet (1, 2) , Léopold Gaichies (1, 2) , Corinne Jeanne (3) , Céline Bazille (4) , Mélanie Briand (2, 5, 3) , Mégane Vernon (2, 5, 3) , Florence Giffard (2, 3) , Frédéric Leprêtre (6) , Laurent Poulain (2, 5, 7) , Christophe Denoyelle (2, 5, 8) , Nicolas Vigneron (2, 3) , Raffaèle Fauvet (2)

1 UNICAEN Santé - Université de Caen Normandie - UFR Santé
2 ANTICIPE - Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers
3 UNICANCER/CRLC - Centre Régional de Lutte contre le Cancer François Baclesse [Caen]
4 CHU Caen
5 UNICAEN - Université de Caen Normandie
6 PLBS - Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41
7 ICM - UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle
8 UNICANCER

Epithelial ovarian cancers (EOCs) are a heterogeneous collection of malignancies, each with their own developmental origin, clinical behavior and molecular profile. With less than 5% of EOC cases, mucinous ovarian carcinoma is a rare form with a poor prognosis and a 5-year survival of 11% for advanced stages (III/IV). At the early stages, these malignant forms are clinically difficult to distinguish from borderline (15%) and benign (80%) forms with a better prognosis due to the large size and heterogeneity of mucinous tumors. Improving their diagnosis is therefore a challenge with regard to the risk of under-treating a malignant form or of unnecessarily undertaking radical surgical excision. The involvement of microRNAs (miRNAs) in tumor progression and their potential as biomarkers of diagnosis are becoming increasingly recognized. In this study, the comparison of miRNA microarray expression profiles between malignant and borderline tumor FFPE samples identified 10 down-regulated and 5 up-regulated malignant miRNAs, which were validated by individual RT-qPCR. To overcome normalization issues and to improve the accuracy of the results, a ratio analysis combining paired up-regulated and down-regulated miRNAs was performed. Although 21/50 miRNA expression ratios were significantly different between malignant and borderline tumor samples, any ratio could perfectly discriminate the two groups. However, a combination of 14 pairs of miRNA ratios (double ratio) showed high discriminatory potential, with 100% of accuracy in distinguishing malignant and borderline ovarian tumors, which suggests that miRNAs may hold significant clinical potential as a diagnostic tool. In summary, these ratio miRNA-based signatures may help to improve the precision of histological diagnosis, likely to provide a preoperative diagnosis in order to adapt surgical procedures.

Mots clés: microRNA; ratio; ovarian carcinoma; mucinous ovarian cancer; mucinous borderline ovarian tumor; cancer diagnosis

Domaines: Sciences du Vivant [q-bio]

Enora Dolivet, Léopold Gaichies, Corinne Jeanne, Céline Bazille, Mélanie Briand, et al.. Synergy of the microRNA Ratio as a Promising Diagnosis Biomarker for Mucinous Borderline and Malignant Ovarian Tumors. International Journal of Molecular Sciences, 2023, International Journal of Molecular Sciences, 24 (21), pp.16016. ⟨10.3390/ijms242116016⟩. ⟨hal-04481385⟩