Predictive Relevance of Circulating miR-622 in Patients with Newly Diagnosed and Recurrent High-Grade Serous Ovarian Carcinoma

Nicolas Vigneron (1, 2, 3, 4, 5) , Mégane Vernon (1, 4, 3, 5, 2) , Matthieu Meryet-Figuière (2, 4, 3, 5, 1) , Bernard Lambert (1, 2, 6, 4, 3, 5) , Mélanie Briand (1, 2, 4, 3, 5) , Marie-Hélène Louis (1, 2, 4, 3, 5) , Sophie Krieger (1, 2, 4, 3) , Florence Joly (1, 2, 4, 3) , Stéphanie Lheureux (7) , Cécile Blanc-Fournier (1, 2, 4, 5) , Pascal Gauduchon (1, 2, 4, 3, 5) , Laurent Poulain (1, 2, 4, 3, 5) , Christophe Denoyelle (1, 2, 4, 3, 5)

1 ANTICIPE - Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers
2 UNICANCER/CRLC - Centre Régional de Lutte contre le Cancer François Baclesse [Caen]
3 UNICAEN - Université de Caen Normandie
4 INSERM - Institut National de la Santé et de la Recherche Médicale
5 Axe BioTICLA
6 CNRS-L - National Council for Scientific Research = Conseil national de la recherche scientifique du Liban [Lebanon]
7 Princess Margaret Hospital

Background Identifying patients with high-grade serous ovarian cancer (HGSOC) who will respond to treatment remains a clinical challenge. We focused on miR-622, a miRNA involved in the homologous recombination repair (HRR) pathway, and we assessed its predictive value in serum prior to first-line chemotherapy and at relapse. Methods Serum miR-622 expression was assessed in serum prior to first-line platinum-based chemotherapy in a prospective multicenter study (miRNA Serum Analysis, miRSA, NCT01391351) and a retrospective cohort (Biological Resource Center, BRC), and was also studied at relapse. Progression-free survival (PFS) and overall survival (OS) were used as primary and secondary endpoints prior to first-line chemotherapy and OS as a primary endpoint at relapse. Results The group with high serum miR-622 expression was associated with a significantly lower PFS (15.4 versus 24.4 months; adjusted HR 2.11, 95% CI 1.2 3.8, P = 0.015) and OS (29.7 versus 40.6 months; adjusted HR 7.68, 95% CI 2.2–26.2, P = 0.0011) in the miRSA cohort. In the BRC cohort, a high expression of miR-622 was also associated with a significantly lower OS (22.8 versus 35.9 months; adjusted HR 1.98, 95% CI 1.1–3.6, P = 0.026). At relapse, high serum miR-622 was associated with a significantly lower OS (7.9 versus 20.6 months; adjusted HR 3.15, 95% CI 1.4–7.2, P = 0.0062). Serum miR-622 expression is a predictive independent biomarker of response to platinum-based chemotherapy for newly diagnosed and recurrent HGSOC. Conclusions These results may open new perspectives for HGSOC patient stratification and monitoring of resistance to platinum-based and poly(ADP-ribose)-polymerase-inhibitor-maintenance therapies, facilitating better and personalized treatment decisions.

Domaines: Cancer; Biochimie, Biologie Moléculaire; Sciences du Vivant [q-bio]

Nicolas Vigneron, Mégane Vernon, Matthieu Meryet-Figuière, Bernard Lambert, Mélanie Briand, et al.. Predictive Relevance of Circulating miR-622 in Patients with Newly Diagnosed and Recurrent High-Grade Serous Ovarian Carcinoma. Clinical Chemistry, 2020, ⟨10.1093/clinchem/hvz013⟩. ⟨hal-02465285⟩