Abstract C050: The role of PD-L1, ACKR/DARC, Livin and Annexin A5 in malignant tumours of the bone, prostate, breast, eye/orbit, nasopharynx, and metastatic carcinomas to the brain, neck and lymph node among West Africans in Zaria, Nigeria

Abstract

Abstract Cancer ranks as a leading cause of death and an important barrier to increasing life expectancy worldwide. Globally, there are estimated 19.3 million new cancer cases and about 10 million cancer mortality in 2020. Should current cancer trends continue, Africa’s cancer burden is projected to reach an alarming 1.4 million new cases and 1 million deaths by 2030. Thus, racial/ethnic disparities in cancer morbidity and mortality continue to widen globally but molecular biology and genomic studies rarely interrogate cancer in diverse disadvantaged populations. Effective control of tumour growth in cancer microenvironment is facilitated by cellular interaction between innate and adaptive immune cells. The programmed death ligand-1 (PD-L1), an immune checkpoint expressed on tumour cells, facilitates the escape of immunosurveillance in cancer by interacting with programmed death-1 (PD-1) to initiate apoptosis of the immune cells. The interaction between these immune cells may be mediated by atypical chemokine receptor 1 (ACKR1)/Duffy antigen receptor for chemokines (DARC) towards activation of tumour-specific immune response by chemoattraction of leukocytes to the inflammatory sites. Livin/BIRC7 protein overexpression is a key component of evasion of apoptosis in cancer cells. Interestingly, Annexin A5, an important member of Annexin family of proteins with high affinity to phosphatidylserine, has been reported to serve as an important component of apoptosis by stimulating immunogenicity of tumor cells. In this pilot study, we report using immunohistochemistry, RNA-seq and whole exome sequencing the expression pattern and functional significance of PD-L1, ACKR/DARC, Livin/BIRC7 and Annexin A5 in malignant tumours of the bone, prostate, breast, eye/orbit, nasopharynx, and metastatic carcinomas to the brain, neck and lymph node among West Africans in Zaria, Nigeria. In osteosarcoma and osteogenic sarcoma of the bone, we observed negative expression of ACKR/DARC and PD-L1, and overexpression of Livin and Annexin A5 proteins. However, a mucoepidermoid carcinoma of the index finger shows strong expression of ACKR/DARC, PD-L1 and Annexin A5 with poor expression of Livin protein. The results also show negative expression of ACKR/DARC, PD-L1 and Livin proteins from retinoblastoma, nasopharyngeal carcinoma, metastatic adenosquamous carcinoma to the parietal lobe of the brain, Metastatic squamous neck cancer, metastatic carcinoma of the lymph nodes and invasive breast carcinoma no special type (NST) grade 3. Prostate adenocarcinomas with Gleason grade 9 show negative expression of ACKR/DARC and PD-L1 proteins. All the tumours studied are strongly positive for Annexin A5 expression. The diverse expression pattern of ACKR/DARC, PD-L1, Livin and Annexin A5 in malignant tumours of the bone, retina, nasopharynx, breast, prostate and metastatic carcinomas to the brain, neck and lymph may be of significant importance in tumour behaviour and prognosis. Citation Format: Faruk Mohammed, Melissa B. Davis, Clayton C. Yates, Halimatu Sadiya Musa. The role of PD-L1, ACKR/DARC, Livin and Annexin A5 in malignant tumours of the bone, prostate, breast, eye/orbit, nasopharynx, and metastatic carcinomas to the brain, neck and lymph node among West Africans in Zaria, Nigeria [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C050.