期刊
CLINICAL CANCER RESEARCH
卷 13, 期 24, 页码 7413-7420出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-07-1083
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资金
- Medical Research Council [G0200103] Funding Source: researchfish
- MRC [G0200103] Funding Source: UKRI
- Medical Research Council [G0200103] Funding Source: Medline
- Breast Cancer Now [2003:596] Funding Source: Medline
Purpose:We investigated whether BRCA1 m RNA 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 rnRNA 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 rnRNA expression as a predictive marker of survival in sporadic epithelial ovarian cancer.
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