BRCA1 mRNA Expression Levels Predict for Overall Survival in Ovarian Cancer after Chemotherapy

• Published in: Clinical cancer research 2007-12, Vol.13 (24), p.7413-7420
• Main Authors: Quinn, Jennifer E, James, Colin R, Stewart, Gail E, Mulligan, Jude M, White, Patricia, Chang, Gary K F, Mullan, Paul B, Johnston, Patrick G, Wilson, Richard H, Harkin, D Paul
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - therapeutic use; Apoptosis; Apoptosis - genetics; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Blotting, Western; BRCA1; BRCA1 Protein - biosynthesis; BRCA1 Protein - genetics; Cisplatin; Docetaxel; Drug Resistance, Neoplasm - genetics; Female; Flow Cytometry; Humans; Kaplan-Meier Estimate; Middle Aged; Neoplasms, Glandular and Epithelial - drug therapy; Neoplasms, Glandular and Epithelial - genetics; Neoplasms, Glandular and Epithelial - mortality; Ovarian Cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - genetics; Ovarian Neoplasms - mortality; Overall Survival; Paclitaxel; Polymerase Chain Reaction; Predictive Marker; RNA, Messenger - analysis; Survival Analysis
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-07-1083

Purpose: We investigated whether BRCA1 mRNA expression levels may represent a biomarker of survival in sporadic epithelial ovarian cancer following chemotherapy treatment. Experimental Design: The effect of loss of BRCA1 expression on chemotherapy response in ovarian cancer was measured in vitro using dose inhibition assays and Annexin V flow cytometry. Univariate and multivariate analyses were done to evaluate the relationship between BRCA1 mRNA expression levels and survival after chemotherapy treatment in 70 fresh frozen ovarian tumors. Results: We show that inhibition of endogenous BRCA1 expression in ovarian cancer cell lines results in increased sensitivity to platinum therapy and decreased sensitivity to antimicrotubule agents. In addition, we show that patients with low/intermediate levels of BRCA1 mRNA have a significantly improved overall survival following treatment with platinum-based chemotherapy in comparison with patients with high levels of BRCA1 mRNA (57.2 versus 18.2 months; P = 0.0017; hazard ratio, 2.9). Furthermore, overall median survival for higher- BRCA1 -expressing patients was found to increase following taxane-containing chemotherapy (23.0 versus 18.2 months; P = 0.12; hazard ratio, 0.53). Conclusions: We provide evidence to support a role for BRCA1 mRNA expression as a predictive marker of survival in sporadic epithelial ovarian cancer.