Abstract 3475: Progranulin as a prognostic biomarker of advanced epithelial ovarian cancer.

Abstract

Abstract Late diagnosis and early recurrence make epithelial ovarian cancer (EOC) the leading cause of gynecologic cancer death in the US. Indicators of early relapse may allow triage of high-risk patients to earlier therapy. Progranulin (PGRN) is a growth and survival factor overexpressed in EOC. We hypothesize that elevated serum (s)PGRN concentrations after clinical complete response (CCR) to primary platinum and taxane-based combination chemotherapy prognosticates disease recurrence and decreased survival in advanced EOC patients. We previously demonstrated high plasma (p)PGRN concentration (cutoff 59ng/ml) at first CCR distinguished early from late recurrence and predicted long-term survival (ROC AUC=0.944; sensitivity 93%; specificity 100%). In multivariate analysis, high pPGRN concentration predicted early recurrence (HR=23.5; 95%CI: 2.49-221; P<0.006). As PGRN is cleaved into proinflammatory granulins by neutrophil elastase, we wished to investigate the reliability of sPGRN as a biomarker. We compared PRGN concentrations in ten blinded, paired serum and plasma samples, using commercial PRGN ELISA assays; paired two-tailed t-test demonstrated comparability (P=0.90, R2= 0.002). A cohort of 35 blinded serum samples from a different institution was analyzed using the ELISA. The optimal dichotomization concentration of sPGRN, 49.5ng/ml, was determined by ROC statistics at a specificity of 90%, and applied to outcome analyses using Cox proportional hazards and Kaplan-Meier modeling. This PGRN cutoff significantly differentiated progression-free survival (PFS; P=0.0013). Subjects with low sPGRN had 100% survival (OS) at 2 years (N=11; range 2-12). Further validation of PGRN's discriminatory value could lead to its clinical investigation as a prognostic biomarker to stratify those at high risk for recurrence to closer monitoring or maintenance therapy, as well as its examination as a predictive biomarker for response to initial therapy. Citation Format: Sharon Fitzgerald, Minshu Yu, John Hays, Nicola Di Santo, Laura Havrilesky, Elise Kohn. Progranulin as a prognostic biomarker of advanced epithelial 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 3475. doi:10.1158/1538-7445.AM2013-3475