Abstract 2638: Overexpressions of cortisol, annexin V and Lost in expression of PD-L1 and DARC proteins are associated with aggressive prostate cancer phenotypes in Black men: A CaPTC Cohort Study

Prostate cancer (CaP) is the most common male gender cancer and present with a 5-year prevalence, incidence and mortality rate in Nigerian Black men. There is disproportionate prevalence and poor understanding of CaP in Black men globally. The Prostate Cancer Transatlantic Consortium (CaPTC) has documented significant CaP burden among Nigerian black men in Nigeria and in the Diaspora. Notably, African ancestry is one of the most important risk factors of CaP globally. Increased levels of cortisol, a stress-related catabolic hormone is significantly associated to prostate specific antigen and poor prognosis in prostate cancer patients. Cortisol causes degradation of muscle proteins into amino-acids. Amino acids such as leucine, serves as a source of fuel for aggressive prostate cancer cells in a Warburg effect model through the L-amino acid transporters (LATs). The annexins are calcium and phospholipid binding proteins implicated in cancer development and progression. Overexpression of annexin 1 is one of the mechanisms by which cortisol inhibit inflammation. Annexin V has a high affinity to phosphatidylserine and play important role of inhibiting engulfment of apoptotic cells by macrophages to increase the immunogenicity of tumor cells undergoing apoptosis. PD-L1 is an important membrane-bound costimulatory molecule that inhibits immune responses through its receptor, PD-1. Overexpression of PD-L1 results to cancer cells aggressively evading the host immune system. The Duffy Antigen/Receptor for Chemokines (DARC) is a 7-transmembrane protein atypical chemokine receptor expressed on erythrocytes and vascular endothelial cells that binds to and clears angiogenic chemokines. Expression pattern of DARC is associated to cancer growth and metastasis. In this study, we report the expression pattern of tissue Cortisol, Annexin V, PD-L1 and DARC proteins in relationship to Gleason score in Nigerian Black men with Prostate cancer using immunohistochemistry and immunofluorescence. In addition, we assessed salivary cortisol levels by enzyme immunoassay and physical activity by a standardized CaPTC-AC3-MADCaP (C.A.M) CaP measures from 500 subjects recruited by via CaPTC cohort. Results showed significant expression of tissue and salivary cortisol in the CaP patients compared to the normal subjects (p u003e 0.05). The Tissue cortisol protein expression was higher in CaP cases with Gleason score 8. There was significant overexpression of Annexin protein in virtually the prostate cancer samples studied. We found a negative expression of PD-L1 and DARC proteins in all the CaP tissues studied. Cortisol and Annexin may serve as an important biomarker for prostate cancer diagnosis and prognosis in Nigerian Blacks. Citation Format: Faruk Mohammed, Folakemi T. Odedina, Sani Ibrahim, Abdulmumini Hassan Rafindadi, Ahmed Adamu, Abdullahi Adamu, Ahmad Bello, Surajo Mohammed Aminu, John Idoko, Aishatu Maude Suleiman, Solomon O. Rotimi, Ernie Kaninjing, Getachew A. Dagne, Clayton Yates, Yawale Iliyasu, Nissa Askins, Iya Eze Bassey, Renee Reams, Abdullahi Mohammad, Hussaini Yusuf Maitama, Dauda Maigatari, Mohammed Sani Shehu, Cheh Augustine Awasum, Abdulkadir Lawal Rafinadadi, Danladi Amodu Ameh, Serah Adewunmi, Ruth Agaba, Haruna Mohammad Muktar, Ahmad Mai, Saad Aliyu Ahmed, Ahmad Bello Kumo, Kasimu Umar Adoke, Ahmad Tijjani Lawal, Ahmad Muhammad, Omolora Fatiregun, Sunday Atawodi, Shehu Akuyam, Yusuf Abdulrashid, Mubarak Liman, Aliyu Muhammad, Abidemi Omonisi, Rebecca Gali, Hassan Dogo, Nkegoum Blaise, Anthonia Sowunmi, Titilola Akinremi, Emeka J. Iweala, Jigo Dangude Yaro, Badejo Adebukola Catherine, Akinwumi Oluwole Komolafe. Overexpressions of cortisol, annexin V and Lost in expression of PD-L1 and DARC proteins are associated with aggressive prostate cancer phenotypes in Black men: A CaPTC Cohort Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2638.