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


Journal

Clinical chemistry
ISSN: 1530-8561
Titre abrégé: Clin Chem
Pays: England
ID NLM: 9421549

Informations de publication

Date de publication:
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

352-362

Informations de copyright

© American Association for Clinical Chemistry 2020.

Auteurs

Nicolas Vigneron (N)

Normandie Université, UNICAEN, Inserm U1086 ANTICIPE, Biology and Innovative Therapeutics for Ovarian Cancer (BioTICLA), Caen, France.
UNICANCER, Cancer Center F. Baclesse, Caen, France.

Mégane Vernon (M)

Normandie Université, UNICAEN, Inserm U1086 ANTICIPE, Biology and Innovative Therapeutics for Ovarian Cancer (BioTICLA), Caen, France.
UNICANCER, Cancer Center F. Baclesse, Caen, France.

Matthieu Meryet-Figuière (M)

Normandie Université, UNICAEN, Inserm U1086 ANTICIPE, Biology and Innovative Therapeutics for Ovarian Cancer (BioTICLA), Caen, France.
UNICANCER, Cancer Center F. Baclesse, Caen, France.

Bernard Lambert (B)

Normandie Université, UNICAEN, Inserm U1086 ANTICIPE, Biology and Innovative Therapeutics for Ovarian Cancer (BioTICLA), Caen, France.
UNICANCER, Cancer Center F. Baclesse, Caen, France.
CNRS, Normandy Delegation, France.

Mélanie Briand (M)

Normandie Université, UNICAEN, Inserm U1086 ANTICIPE, Biology and Innovative Therapeutics for Ovarian Cancer (BioTICLA), Caen, France.
UNICANCER, Cancer Center F. Baclesse, Caen, France.

Marie-Hélène Louis (MH)

Normandie Université, UNICAEN, Inserm U1086 ANTICIPE, Biology and Innovative Therapeutics for Ovarian Cancer (BioTICLA), Caen, France.
UNICANCER, Cancer Center F. Baclesse, Caen, France.

Sophie Krieger (S)

UNICANCER, Cancer Center F. Baclesse, Caen, France.
UNICANCER, Cancer Center F. Baclesse, Biopathology Department, Caen, France.
Normandie Université, UNIROUEN, Inserm U1245, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Florence Joly (F)

Normandie Université, UNICAEN, Inserm U1086 ANTICIPE, Biology and Innovative Therapeutics for Ovarian Cancer (BioTICLA), Caen, France.
UNICANCER, Cancer Center F. Baclesse, Caen, France.
UNICANCER, Cancer Center F. Baclesse, Medical Oncology Department and Clinical Research Unit, Caen, France.

Stéphanie Lheureux (S)

Division of Medical Oncology and Hematology, Princess Margaret Cancer Center, Toronto, ON, Canada.

Cécile Blanc-Fournier (C)

UNICANCER, Cancer Center F. Baclesse, Caen, France.
UNICANCER, Cancer Center F. Baclesse, Biopathology Department, Caen, France.

Pascal Gauduchon (P)

Normandie Université, UNICAEN, Inserm U1086 ANTICIPE, Biology and Innovative Therapeutics for Ovarian Cancer (BioTICLA), Caen, France.
UNICANCER, Cancer Center F. Baclesse, Caen, France.

Laurent Poulain (L)

Normandie Université, UNICAEN, Inserm U1086 ANTICIPE, Biology and Innovative Therapeutics for Ovarian Cancer (BioTICLA), Caen, France.
UNICANCER, Cancer Center F. Baclesse, Caen, France.

Christophe Denoyelle (C)

Normandie Université, UNICAEN, Inserm U1086 ANTICIPE, Biology and Innovative Therapeutics for Ovarian Cancer (BioTICLA), Caen, France.
UNICANCER, Cancer Center F. Baclesse, Caen, France.

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