Clinical validation of chemotherapy predictors developed on global microRNA expression in the NCI60 cell line panel tested in ovarian cancer

• Published in: PloS one 2017-03, Vol.12 (3), p.e0174300
• Main Authors: Prahm, Kira Philipsen, Høgdall, Claus, Karlsen, Mona Aarenstrup, Christensen, Ib Jarle, Novotny, Guy Wayne, Knudsen, Steen, Hansen, Anker, Jensen, Peter Buhl, Jensen, Thomas, Mirza, Mansoor Raza, Ekmann-Gade, Anne Weng, Nedergaard, Lotte, Høgdall, Estrid
• Format: Article
• Language: English
• Subjects: Aged; Antineoplastic Agents - therapeutic use; Antineoplastic Agents, Phytogenic - therapeutic use; Biology and life sciences; Cancer; Cancer therapies; Carboplatin; Carboplatin - therapeutic use; Cell Line, Tumor; Chemoresistance; Chemotherapy; Correlation; Docetaxel; Drug resistance; Drug Resistance, Neoplasm; Drug therapy; Female; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Genetic aspects; Growth inhibition; Gynecology; Health aspects; Health hazards; Hospitals; Humans; Medical prognosis; Medicine and Health Sciences; MicroRNA; MicroRNAs; MicroRNAs - metabolism; Middle Aged; miRNA; Oligonucleotide Array Sequence Analysis; Oncology; Ovarian cancer; Ovarian carcinoma; Ovarian Neoplasms - diagnosis; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - metabolism; Paclitaxel; Paclitaxel - therapeutic use; Pathology; Patients; Predictions; Prognosis; Ribonucleic acid; RNA; Surgery; Survival; Taxoids - therapeutic use; Tumor cell lines
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0174300

Ovarian cancer is the leading cause of death among gynecologic malignancies. This is partly due to a non-durable response to chemotherapy. Prediction of resistance to chemotherapy could be a key role in more personalized treatment. In the current study we aimed to examine if microRNA based predictors could predict resistance to chemotherapy in ovarian cancer, and to investigate if the predictors could be prognostic factors for progression free and overall survival. Predictors of chemotherapy-resistance were developed based on correlation between miRNA expression and differences in measured growth inhibition in a variety of human cancer cell lines in the presence of Carboplatin, Paclitaxel and Docetaxel. These predictors were then, retrospectively, blindly validated in a cohort of 170 epithelial ovarian cancer patients treated with Carboplatin and Paclitaxel or Docetaxel as first line treatment. In a multivariate cox proportional analysis the predictors of chemotherapy-resistance were not able to predict time to progression after end of chemotherapy (hazard ratio: 0.64, 95% CI: 0.36-1.12, P = 0.117). However, in a multivariate logistic analysis, where time to progression was considered as either more or less than 6 months, the predictors match clinical observed chemotherapy-resistance (odds ratio: 0.19, 95% CI: 0.05-0.73, P = 0.015). Neither univariate nor multivariate, time-dependent, cox analysis for progression free survival (PFS) or overall survival (OS) in all 170 patients showed to match predicted resistance to chemotherapy (PFS: hazard ratio: 0.69, 95% CI: 0.40-1.19, P = 0.183, OS: hazard ratio: 0.76, 95% CI: 0.42-1.40, P = 0.386). In the current study, microRNA based predictors of chemotherapy-resistance did not demonstrate any convincing correlation to clinical observed chemotherapy-resistance, progression free survival, or overall survival, in patients with epithelial ovarian cancer. However the predictors did reflect relapse more or less than 6 months.