Comparative analysis of predictive values of the kinetics of 11 circulating miRNAs and of CA125 in ovarian cancer during first line treatment (a GINECO study)

Gynecol Oncol. 2020 Oct;159(1):256-263. doi: 10.1016/j.ygyno.2020.07.021. Epub 2020 Jul 22.

Abstract

Objective: MicroRNAs (miRNAs) are promising biomarkers in ovarian cancer. Their kinetics during treatment might be useful for monitoring disease burden, and guiding treatments in patients treated with peri-operative chemotherapy and interval debulking surgery (IDS).

Methods: Serial blood samples of patients enrolled in the randomized phase II CHIVA trial, comparing first line carboplatin-paclitaxel +/- nintedanib (NCT01583322) and IDS, were investigated to assess the kinetics of 11 relevant miRNAs. Their prognostic/predictive values regarding the likelihood of complete IDS, and the patient survival, were assessed and compared to those of CA125 kinetics. The selection of the miRNAs (miR-15b-5p, miR-16-5p, miR-20a-5p, miR-21-5p, miR-93-5p, miR-122-5p, miR-150-5p, miR-195-5p, miR-200b-3p, miR-148b-5p and miR-34a-5p) was based on the expression levels found with a large explorative panel, and on the literature data.

Results: 756 serial blood samples from 119 patients were analyzed for a total of 8172 miRNA assays, and 1299 CA125 values. The longitudinal kinetics of the miRNA expressions were highly inconsistent, and were not related to CA125 dynamics. The miRNA changes during neoadjuvant treatment were not found associated with RECIST tumor response or IDS outcomes. Decreases of miR-34a-5p and miR-93-5p were associated with PFS benefit (p = .009) and OS benefits (p < .001), respectively, using univariate tests.

Conclusions: The longitudinal kinetics of miRNA expressions during neoadjuvant treatment in ovarian cancer patients were inconsistent, and were not found to be associated with tumor burden changes. Although some prognostic value could be discussed, no predictive value regarding tumor responses or IDS quality could be identified.

Keywords: Biomarkers; Chemotherapy; Ovarian cancer; Prognosis; ca125; miRNA.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / blood*
  • CA-125 Antigen / blood*
  • Carboplatin / therapeutic use
  • Circulating MicroRNA / blood*
  • Cytoreduction Surgical Procedures
  • Female
  • Humans
  • Indoles / therapeutic use
  • Kinetics
  • Membrane Proteins / blood*
  • Middle Aged
  • Neoadjuvant Therapy
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / therapy
  • Paclitaxel / therapeutic use
  • Predictive Value of Tests
  • Prognosis
  • Progression-Free Survival
  • Response Evaluation Criteria in Solid Tumors

Substances

  • Biomarkers, Tumor
  • CA-125 Antigen
  • Circulating MicroRNA
  • Indoles
  • MUC16 protein, human
  • Membrane Proteins
  • Carboplatin
  • nintedanib
  • Paclitaxel

Associated data

  • ClinicalTrials.gov/NCT01583322