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. Methods We measured miRNA concentrations in plasma samples from 14 patients with platinumresistant, 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). 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. 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.
| Original language | English (US) |
|---|---|
| Article number | e0141279 |
| Journal | PloS one |
| Volume | 10 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 20 2015 |
Funding
This work was partly funded by the National Cancer Institute Award CA133877-01 (DM), NCI-CA182832 (DM & KPN), National Institute of General Medical Sciences 5T32GM008425-19 (EAB) and the Indiana University Simon Cancer Center Cancer Center Support Grant P30 CA082709-15 supporting the Bioinformatics core. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors thank Eisai Co., Ltd. (Tokyo, Japan) for providing decitabine, Mrs. Amber Allen, Carol Kulesavage, Nancy Menning, and Jessica Roy for coordination of clinical trial activities. Dr. Matei reports grants from NCI, other from Eisai, during the conduct of the study; personal fees from Astra Zenecca, grants from US Department of Veterans Affairs, grants from V Foundation, and grants from NCI, outside the submitted work. Dr. Benson reports grants from National Institute of Health, NIGMS, during the conduct of the study. Dr. Nephew reports NCI and V foundation grants. The other authors have no relevant conflict of interest. Eisai Co., Ltd. (Tokyo, Japan) provided decitabine for this study. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.
ASJC Scopus subject areas
- General
