BRCA1 mRNA expression levels predict for overall survival in ovarian cancer after chemotherapy
Autor: | Jennifer E. Quinn, G. K. F. Chang, Patrick G. Johnston, Richard H. Wilson, Paul B. Mullan, Jude M. Mulligan, Patricia M White, Colin R. James, D. P. Harkin, Gail E. Stewart |
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Rok vydání: | 2007 |
Předmět: |
Oncology
Cancer Research medicine.medical_specialty endocrine system diseases medicine.medical_treatment Blotting Western Antineoplastic Agents Apoptosis Kaplan-Meier Estimate Biology Polymerase Chain Reaction Flow cytometry Internal medicine medicine Biomarkers Tumor Humans Neoplasms Glandular and Epithelial RNA Messenger Survival analysis Ovarian Neoplasms Chemotherapy Predictive marker medicine.diagnostic_test BRCA1 Protein Hazard ratio Middle Aged medicine.disease Flow Cytometry Survival Analysis Drug Resistance Neoplasm Biomarker (medicine) Female Ovarian cancer |
Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 13(24) |
ISSN: | 1078-0432 |
Popis: | 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. |
Databáze: | OpenAIRE |
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