Abstract 7: Berg Interrogative Biology™ platform unravels novel biomarkers FLNB and LY9 in combination with PSA enhances specificity in serum of patients with prostate cancer.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Prostate Specific Antigen (PSA) test is the predominant screening test for prostate cancer. Utility is limited by the low predictive power to differentiate patients with indolent tumors from aggressive disease with potential for metastasis. Identification of potential biomarkers to increase prediction of patient population with propensity for progression to metastatic disease remains the overarching unmet need in prostate cancer screening. This study reports the identification of a panel of potential biomarkers using the Berg Interrogative Biology™ platform, a novel non-hypothesis driven approach to characterize disease specific molecular signatures for the identification of physiological drivers of disease etiology. Filamin B (FLNB) and lymphocyte antigen 9 (LY9) were two of several markers identified from a high confidence causal network of prostate cancer model using the Berg Interrogative Biology™ platform. Both FLNB and LY9 were validated in a small case-control retrospective study in human serum samples of patients with prostate cancer and age-matched normal controls. The utility of FLNB and LY9 as potential biomarkers in prostate cancer was determined by comparing the serum levels to that of PSA to establish benchmark comparison. Statistically significant elevation of the PSA, FLNB, and LY9 concentrations was detected in the prostate cancer group compared to the age-matched normal control group. Statistical analyses were performed to determine the sensitivity and specificity of the molecular markers by ROC curve analysis. The predictive power of FLNB or LY9 alone was comparable to that of the PSA test. The combination of FLNB and LY9 with PSA out-performed PSA alone with AUC=0.975 in the study. The study provides data in support of FLNB and LY9 as biomarkers with potential to improve screening outcomes when used in combination with PSA. Efforts are currently underway in large patient cohorts to validate the clinical utility of FLNB and LY9 as candidate biomarkers for use in the screening of prostate cancer with correlate to the Gleason score to enable more instructive data to the practitioner. Citation Format: Rangaprasad Sarangarajan, Joyce Chan, Eric Grund, Vivek K. Vishnudas, Shen Luan, Viatcheslav R. Akmaev, Niven R. Narain. Berg Interrogative Biology ™ platform unravels novel biomarkers FLNB and LY9 in combination with PSA enhances specificity in serum of patients with prostate 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 7. doi:10.1158/1538-7445.AM2013-7