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SHR Neuro Cancer Cardio Lipid Metab Microb

Tsibulak, I; Wieser, V; Degasper, C; Shivalingaiah, G; Wenzel, S; Sprung, S; Lax, SF; Marth, C; Fiegl, H; Zeimet, AG.
BRCA1 and BRCA2 mRNA-expression prove to be of clinical impact in ovarian cancer.
Br J Cancer. 2018; 119(6):683-692 Doi: 10.1038/s41416-018-0217-4 [OPEN ACCESS]
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Abstract:: Mutations in BRCA1 and BRCA2 are associated with better survival in ovarian cancer (OC) patients due to a better response to platinum-based chemotherapy. However, the impact of the BRCA1/2 mRNA-expression is not well characterized in OC. We investigated BRCA1/2 mRNA-expression in 12 non-neoplastic fallopian tubes and 201 epithelial OCs in relation to their clinical characteristics. We found higher BRCA1/2 mRNA-expression in OCs compared to controls (P = 0.011, P < 0.001, respectively). BRCA1 mutated OCs exhibited lower BRCA1 (P = 0.014) but higher BRCA2 mRNA-expression (P = 0.001). Low BRCA1-expression was associated with favorable overall survival (OS) (P = 0.012) and low BRCA2-expression with better progression-free survival (PFS) and OS (P = 0.004, P = 0.001, respectively). A subgroup-analysis showed that this effect was confined only to the BRCA1-wildtype cancers. Cox-regression confirmed the prognostic significance of BRCA1-expression for OS (P = 0.028). Independency of the prognostic value of BRCA2-expression for PFS (P = 0.045) and OS (P = 0.015) was restricted to high-grade serous OCs. Fully platinum-sensitivity was characterized by lower BRCA1/2 mRNA-expression in BRCA1-wildtype cancers in comparison to platinum-refractory OC. Our findings may reflect higher platinum-sensitivity due to reduced capacity of DNA damage repair in tissues with low BRCA1/2-expression. In this context, especially in BRCA-wildtype cancers both parameters could also be potential predictors for PARP-sensitivity.
Find related publications in this database (using NLM MeSH Indexing): Adult -; Aged -; Aged, 80 and over -; BRCA1 Protein - genetics; BRCA2 Protein - genetics; Carcinoma, Ovarian Epithelial - drug therapy; Carcinoma, Ovarian Epithelial - genetics; Carcinoma, Ovarian Epithelial - pathology; Carcinoma, Ovarian Epithelial - surgery; Case-Control Studies -; Cytoreduction Surgical Procedures -; Disease-Free Survival -; Female -; Gene Expression Profiling -; Gene Expression Regulation, Neoplastic -; Humans -; Middle Aged -; Mutation -; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; Ovarian Neoplasms - surgery; Platinum - therapeutic use; Prognosis -; Treatment Outcome -; Up-Regulation -