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Carboplatin with Decitabine Therapy, in Recurrent Platinum Resistant Ovarian Cancer, Alters Circulating miRNAs Concentrations: A Pilot Study.

Authors :
Benson EA
Skaar TC
Liu Y
Nephew KP
Matei D
Source :
PloS one [PLoS One] 2015 Oct 20; Vol. 10 (10), pp. e0141279. Date of Electronic Publication: 2015 Oct 20 (Print Publication: 2015).
Publication Year :
2015

Abstract

Objective: Plasma miRNAs represent potential minimally invasive biomarkers to monitor and predict outcomes from chemotherapy. The primary goal of the current study-consisting of patients with recurrent, platinum-resistant ovarian cancer-was to identify the changes in circulating miRNA concentrations associated with decitabine followed by carboplatin chemotherapy treatment. A secondary goal was to associate clinical response with changes in circulating miRNA concentration.<br />Methods: We measured miRNA concentrations in plasma samples from 14 patients with platinum-resistant, recurrent ovarian cancer enrolled in a phase II clinical trial that were treated with a low dose of the hypomethylating agent (HMA) decitabine for 5 days followed by carboplatin on day 8. The primary endpoint was to determine chemotherapy-associated changes in plasma miRNA concentrations. The secondary endpoint was to correlate miRNA changes with clinical response as measured by progression free survival (PFS).<br />Results: Seventy-eight miRNA plasma concentrations were measured at baseline (before treatment) and at the end of the first cycle of treatment (day 29). Of these, 10 miRNAs (miR-193a-5p, miR-375, miR-339-3p, miR-340-5p, miR-532-3p, miR-133a-3p, miR-25-3p, miR-10a-5p, miR-616-5p, and miR-148b-5p) displayed fold changes in concentration ranging from -2.9 to 4 (p<0.05), in recurrent platinum resistant ovarian cancer patients, that were associated with response to decitabine followed by carboplatin chemotherapy. Furthermore, lower concentrations of miR-148b-5p after this chemotherapy regimen were associated (P<0.05) with the PFS.<br />Conclusions: This is the first report demonstrating altered circulating miRNA concentrations following a combination platinum plus HMA chemotherapy regiment. In addition, circulating miR-148b-5p concentrations were associated with PFS and may represent a novel biomarker of therapeutic response, with this chemotherapy regimen, in women with recurrent, drug-resistant ovarian cancer.

Details

Language :
English
ISSN :
1932-6203
Volume :
10
Issue :
10
Database :
MEDLINE
Journal :
PloS one
Publication Type :
Academic Journal
Accession number :
26485143
Full Text :
https://doi.org/10.1371/journal.pone.0141279