title: Plasma miR-200b in ovarian carcinoma patients: distinct pattern of pre/post-treatment variation compared to CA-125 and potential for prediction of progression-free survival.
abstract: Ovarian carcinomas (OvCa) are highly heterogeneous malignancies. We investigated four circulating plasma microRNAs (miR-21, miR-34a, miR-200b and miR-205) as candidate biomarkers. Using qPCR, we assessed the plasma concentration of these markers in 101 women, including 51 previously untreated OvCa patients, 25 healthy women and 25 patients bearing benign pelvic lesions. For a subset of 33 OvCa patients, the assay was repeated at the end of the primary treatment. The pattern of variations (post- minus pre-treatment) of concentration was compared to that of CA-125. A Cox regression model was used to study the association between variations and the progression-free survival (PFS). Plasma miR-200b proved to have a greater average concentration in OvCa samples (median 2-ΔΔCt = 15.18) than in samples linked to non-malignant lesions (median 2-ΔΔCt = 1.26, p-value = 0.0004). Its concentration was highly heterogeneous among OvCa patients, without any correlations with the FIGO stage and the pre-treatment CA-125 level. The decrease in CA-125 concentration was constant and often dramatic, while the variations of miR-200b concentration were much more diverse. The variation of miR-200b was marginally associated with the PFS (hazard ratio=2.95 95%CI=[0.94; 9.28], p=0.06) while miR-200b as a continuous time-dependent variable was significantly associated (HR=1.06 [1.02; 1.10], p=0.003). This study is the first direct empirical evidence that miR-200b can provide additional information, independent of CA-125 in OvCa patients.
authors.affiliation: UMR8126 CNRS, Université Paris-Sud, Université Paris-Saclay, Gustave Roussy, F-94805, Villejuif, France.
authors.forename: Nikiforos-Ioannis
authors.initials: NI
authors.lastname: Kapetanakis
authors.affiliation: Department of Surgery, Gustave Roussy, F-94805, Villejuif, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Uzan
authors.affiliation: UMR8126 CNRS, Université Paris-Sud, Université Paris-Saclay, Gustave Roussy, F-94805, Villejuif, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Jimenez-Pailhes
authors.affiliation: Department of Surgery, Gustave Roussy, F-94805, Villejuif, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Gouy
authors.affiliation: Department of Surgery, Gustave Roussy, F-94805, Villejuif, France.
authors.forename: Enrica
authors.initials: E
authors.lastname: Bentivegna
authors.affiliation: Department of Surgery, Gustave Roussy, F-94805, Villejuif, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Morice
authors.affiliation: Department of Oncological Medicine, Gustave Roussy, F-94805, Villejuif, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Caron
authors.affiliation: UMR8126 CNRS, Université Paris-Sud, Université Paris-Saclay, Gustave Roussy, F-94805, Villejuif, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Gourzones-Dmitriev
authors.affiliation: Department of Biostatistics and Epidemiology, Gustave Roussy, F-94805, Villejuif, France.|U1018 INSERM, CESP, Université Paris-Sud, Université Paris-Saclay, F-94085, Villejuif, France.
authors.forename: Gwénaël
authors.initials: G
authors.lastname: Le Teuff
authors.affiliation: UMR8126 CNRS, Université Paris-Sud, Université Paris-Saclay, Gustave Roussy, F-94805, Villejuif, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Busson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D018394:CA-125 Antigen / Q000097:blood*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000097:blood*; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; C533896:MIRN200 microRNA, human; C451759:MUC16 protein, human; D008565:Membrane Proteins; D035683:MicroRNAs
keywords: miR-200b; microRNA; ovarian cancer; plasma; progression-free survival