BRCA1 mRNA expression levels predict for overall survival in ovarian cancer after chemotherapy.
OBJECTIVE
We investigated whether BRCA1 mRNA expression levels may represent a biomarker of survival in sporadic epithelial ovarian cancer following chemotherapy treatment.


METHODS
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.
Quinn
Jennifer E
JE
Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, United Kingdom.
James
Colin R
CR
Stewart
Gail E
GE
Mulligan
Jude M
JM
White
Patricia
P
Chang
Gary K F
GK
Mullan
Paul B
PB
Johnston
Patrick G
PG
Wilson
Richard H
RH
Harkin
D Paul
DP
D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000235:genetics; D019313:BRCA1 Protein / Q000096:biosynthesis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D015153:Blotting, Western; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis*; D016019:Survival Analysis
D000970:Antineoplastic Agents; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D014408:Biomarkers, Tumor; D012333:RNA, Messenger