Predictive Relevance of Circulating miR-622 in Patients with Newly Diagnosed and Recurrent High-Grade Serous Ovarian Carcinoma.
Adult
Aged
Antineoplastic Agents
/ therapeutic use
Cell-Free Nucleic Acids
/ genetics
Disease-Free Survival
Female
Humans
MicroRNAs
/ blood
Middle Aged
Neoplasm Recurrence, Local
/ genetics
Ovarian Neoplasms
/ diagnosis
Poly(ADP-ribose) Polymerase Inhibitors
/ therapeutic use
Prognosis
Progression-Free Survival
Prospective Studies
Retrospective Studies
Circulating miRNA
High-Grade Serous Ovarian Carcinoma
PARP inhibitors
biomarkers
miR-622
platinum
Journal
Clinical chemistry
ISSN: 1530-8561
Titre abrégé: Clin Chem
Pays: England
ID NLM: 9421549
Informations de publication
Date de publication:
01 02 2020
01 02 2020
Historique:
received:
12
06
2019
accepted:
21
10
2019
entrez:
11
2
2020
pubmed:
11
2
2020
medline:
29
7
2020
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 32040573
pii: 5717995
doi: 10.1093/clinchem/hvz013
doi:
Substances chimiques
Antineoplastic Agents
0
Cell-Free Nucleic Acids
0
MIRN622 microRNA, human
0
MicroRNAs
0
Poly(ADP-ribose) Polymerase Inhibitors
0
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
352-362Informations de copyright
© American Association for Clinical Chemistry 2020.