Abstract 3295: GPRASP1:A novel potential biomarker for neuroendocrine carcinoma

Neuroendocrine differentiation has been observed to correlate with the progression and prognosis of prostate cancer (PCa), gastric cancer and pancreatic cancer, but the mechanisms remain unclear. GPRASP-1, a G protein coupled receptor-associated sorting protein 1, is known as a significant modulator of lysosomal sorting, and functional down-regulation of G- protein coupled receptors by interacting with Beclin2. The GPRASP-1 was originally considered as a serum tumor biomarker for breast cancer and later it was confirmed as a ubiquitous tumor marker among lung, liver and brain cancers. Based on its function as a tumor biomarker, we conducted serum ELISA analysis of GPRASP-1, and correlated results with RNAseq and gene copy numbers among a large cohort of PCa patients. We found overexpression and gene amplification of GPRASP-1 in 24 of 77 patients (31%) with neuroendocrine PCa (NEPCa). The patients with elevated serum GPRASP-1 level had a higher risk of metastasis to liver, lung and lymph nodes. Furthermore, immunohistochemical analysis for GPRASP-1 showed a strong staining of the pathological section from pancreatic neuroendocrine carcinoma patients and their liver metastases. Knocking down of the GPRASP-1 in a NEPCa PC3 cell line showed dramatic downregulation of TACR family, Tachykinin Receptor, which is known to be involved in the neuroinflammation and neurotransmitter transport and cancer proliferation. Our results offer a novel link among GPRASP-1, neuroendocrine differentiation and castration resistance in human PCa. We proposed serum GPRASP-1 can serve as a novel biomarker differentiating cancers with and without neuroendocrine differentiation. (Supported by NSFC projects 81773146; Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, 2017B030301018); JCYJ20170412152943794, JCYJ20170412154619484, JCYJ20170307105128101, JCYJ2017030711041760) Note: This abstract was not presented at the meeting. Citation Format: Minggang Xiong, Fuhao Wang, Haiyen E. Zhau, Xin Huang, Leland Chung, Jian Zhang, Yi Lu. GPRASP1:A novel potential biomarker for neuroendocrine carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3295.