Abstract 3918: Circulating progranulin (GP88/PGRN) level correlates with survival in metastatic breast cancer patients

Abstract

Abstract Current monitoring of therapy response in metastatic breast cancer (MBC) patients is dependent on expensive and time consuming imaging methods that have limited sensitivity to detect disease response in a timely manner. Understanding of real-time biological processes through measurement of circulating disease associated biomarkers may provide a clearer understanding of the disease state and thus aid real-time clinical management of MBC patients. Current biomarkers used in MBC include CA15-3, CA27.29 and CEA. While useful, they have limitations in providing clinicians with a reliable insight into real-time monitoring of disease processes. Thus, addition of new circulating biomarkers may improve the management of MBC patients. We characterized a target biomarker, the 88kDa glycoprotein Progranulin (GP88) expressed in tumor tissue and secreted in the circulation of BC patients. Biological studies have established GP88 as one of the critical drivers for tumor cell proliferation, survival, invasiveness and drug resistance. Clinical studies have demonstrated that elevated GP88 tissue levels are prognostic for poor outcome and that breast cancer patients have a statistically elevated GP88 serum level than healthy individuals. Using tissue and serum tests to detect and quantify GP88 could provide an ideal target for monitoring disease progression in BC patients undergoing therapy. In the present study, we examined whether GP88 serum levels were elevated in MBC patients and whether GP88 serum levels were correlated to patient survival. Under an IRB approved protocol, 92 MBC patients that met the inclusion criteria and were undergoing therapy at the UMGCC Breast Clinic were consented. Clinical and disease characteristics along with serum CA15-3 values were collected as part of the study. Serum samples were collected from each patient during therapy and subsequently the patients were monitored. The serum was stored at -80C until tested for GP88. The validated GP88 assay (A&G Pharmaceutical) is sensitive and linear over 0 to 10ng/ml range. Statistical analysis using Kaplan-Meier functions examined if there is a correlation between GP88 serum level and overall survival. By analyzing the KM plots at different GP88 cut points we identified two populations with distinct survival characteristics. When examined more thoroughly the difference in survival of patients with <60ng/ml and >60ng/ml was statistically significant (P = 0.0002). Correlation analysis of serum GP88 and CA15-3 were performed and will be presented. We conclude that circulating levels of GP88 in MBC patients are correlated with survival. It would appear that patients that can be managed to have a GP88 below 60ng/ml will survive longer. Thus measuring circulating GP88 levels would provide additional information to that available in today's SOC for monitoring. This valuable insight into real-time disease status will assist clinicians in patient management. Citation Format: Ginette Serrero, David Hicks, Binbin Yue, Douglas M. Hawkins, Nancy Tait, Katherine H. Tkaczuk. Circulating progranulin (GP88/PGRN) level correlates with survival in metastatic breast cancer patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3918.