Abstract 3455: Elafin is a candidate biomarker that underlies the similarities between basal-like breast cancer and ovarian cancer.

We recently reported that Elafin, a serine proteinase inhibitor encoded on chromosome 20q12-13.2, is overexpressed and secreted by High grade serous carcinoma of the ovary (HGS-OvCa) and is associated with poor overall survival and chemotherapy resistance. Here we show that Elafin confers a proliferative advantage to HGS-OvCa cells through activation of the MAP kinase pathway. Mutations in the anti-proteinase domain of Elafin did not interfere with its ability to stimulate cell growth. This mitogenic effect can be neutralized by RNA interference, specific antibodies targeting Elafin and small molecule inhibitor against MEK kinase. We also observed that IC50 to cisplatin and paclitaxel are significantly higher in OvCa cell lines (n=11) highly expressing Elafin. A phosphoproteome array among 20 cell lines derived from patient9s ascites samples showed that expression of Elafin significantly correlates with increased expression of RAD50 and STAT5A, two proteins involved in platinum resistance. HGS-OvCa shared genomic features with basal-like breast cancer (BLBC) including frequent TP53 mutations, genomic instability, and poor prognosis. Thus, we looked at the expression of Elafin in BC. A meta-analysis of gene-expression profiling from 7 publicly available BC datasets including more than 1,300 tumors showed that Elafin is significantly highly expressed in BLBC compared to luminal and HER-2 subtypes and this observation has been confirmed by IHC on BC tumors (n=25) and on BC cell lines. Additionally, we observed that RNA interference against Elafin reduces proliferation of BLBC cell lines. Citation Format: Intidhar Labidi-Galy, Adam Clauss, Vivian Ng, Sekhar Duraisamy, Shridar Ganesan, Ronny Drapkin. Elafin is a candidate biomarker that underlies the similarities between basal-like breast cancer and ovarian cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3455. doi:10.1158/1538-7445.AM2013-3455