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

Clin Chem. 2020 Feb 1;66(2):352-362. doi: 10.1093/clinchem/hvz013.

Abstract

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.

Keywords: Circulating miRNA; High-Grade Serous Ovarian Carcinoma; PARP inhibitors; biomarkers; miR-622; platinum.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Cell-Free Nucleic Acids / genetics*
  • Disease-Free Survival
  • Female
  • Humans
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / genetics*
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
  • Prognosis
  • Progression-Free Survival
  • Prospective Studies
  • Retrospective Studies

Substances

  • Antineoplastic Agents
  • Cell-Free Nucleic Acids
  • MIRN622 microRNA, human
  • MicroRNAs
  • Poly(ADP-ribose) Polymerase Inhibitors