Abstract 2830: Secreted protein acidic and rich in cysteine antigen and autoantibodies in sera of prostate cancer patients: Potential use in diagnosis /prognosis

Abstract

Abstract Objectives: Improvements in blood based biomarkers for detecting clinically significant prostate cancer (CaP) or for distinguishing between indolent and aggressive CaP are critical in enhancing the management of this most common non-skin cancer of men in the US. These biomarkers include tumor associated antigens (TAAs) and autoantibodies (AAbs) against TAAs in patient sera. SPARC/Osteonectin is highly expressed in metastatic cancers (glioblastoma, melanoma, breast cancer and prostate cancer) and promotes bone metastasis and epithelial-mesemchymal transition. Our comparative transcriptome analyses of well/moderately differentiated CaP with poorly differentiated CaP, defined SPARC as central node in the network of genes with common regulatory elements (NKXH_NKXH_HOX) associating with poorly differentiated CaP. Further, we reported associations of high levels of SPARC mRNA or protein with Gleason 8-10 or poorly differentiated primary tumors and association with metastatic progression. The aims of this study are: i) Quantify SPARC antigen in the sera CaP patients; ii) Are AAbs against SPARC present in the serum of CaP patients?; iii) Is there a correlation between SPARC AAb level in patient sera and disease status? iii) Does SPARC AAb level vary according to distinct ethnic groups? Methods: Sera from CaP patients and healthy controls were evaluated for SPARC antigen using a commercial enzyme-linked immunosorbent assay (ELISA) kit. AAbs against SPARC were determined by ELISA utilizing recombinant full-length human SPARC protein as a substrate. For evaluation we used Caucasian American (CA, n=117) and African American (AA, n=111) CaP patients comprising Gleason 6-10, and healthy controls (CA, n=52; AA, n=45). Results: SPARC antigen levels in the sera showed a difference in the overall case versus control groups (p=0.0016) and this trend was observed only in AA (p=0.0015) in comparison to CA patients (p=0.1709). SPARC AAbs were detected in the sera and the values were significant in the overall case versus control (p< .0001) and also in CA (p<.0001) and AA (p<.0001) CaP patients with levels significantly lower in patients compared to controls. AAb reactivity for CaP patients was similar between CA and AA groups. Conclusions: This study demonstrated the presence of AAbs against SPARC in CaP patient serum for the first time. Of note, highly significant differences were noted between CaP patient (low) and controls (high) sera, across different ethnic groups. These data suggest further evaluation of SPARC AAbs as a promising serum biomarker for CaP. Source of Funding: This research was supported by the Center for Prostate Disease Research, Uniformed Services University Grant HU0001-10-2-0002. Citation Format: Anshu Rastogi, Andy Martinez, Amina Ali, Shyh-Han Tan, Jennifer Cullen, Yongmei Chen, Gyorgy Petrovics, Albert Dobi, Lakshmi Ravindranath, Denise Young, Isabell Sesterhenn, Jacob Kagan, Sudhir Srivastava, David McLeod, Inger Rosner, Shiv Srivastava, Alagarsamy Srinivasan. Secreted protein acidic and rich in cysteine antigen and autoantibodies in sera of prostate cancer patients: Potential use in diagnosis /prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2830. doi:10.1158/1538-7445.AM2017-2830