OR19-3 Differential Interactions of Vitamin D Binding Protein and Vitamin D Receptor in Different Ethnic Groups with Aggressive Thyroid Cancer

Abstract

Abstract Thyroid cancer affects ethnic groups at different rates and severity. Despite this, thyroid cancer health disparities are still an understudied area. Our laboratory has shown a differential expression of vitamin D binding protein (DBP) in Filipino Americans (FA) versus European Americans (EA) [1]. Higher DBP levels correlate to a better prognosis. A study has revealed a DBP-dependent vitamin D receptor (VDR) promoter activation. In this study, we investigated whether VDR and DBP are expressed differentially in different ethnic groups, such as African Americans (AA), Hispanic Americans (HA), EA, and FA. We were also able to determine the differential DBP polymorphisms, VDR variant expressions, and DBP-VDR interactions within different ethnicities. By PCR-Restriction Fragment Length Polymorphism (PCR-RFLP), we determined a higher frequency of DBP gene polymorphism in FA versus EA. Analyzing the Cancer Genome Atlas (TCGA) thyroid cancer datasets with the UALCAN assay, we found the differential expressions of DBP and VDR genes based on cancer stages, sample types, race, and histological subtypes. By immunohistochemistry, we detected strong nuclear VDR (nVDR) and very low membranous VDR (mVDR) expression that correlated with low DBP in FA thyroid cancer tissues. In contrast, there was a higher expression of both mVDR and DBP in HA versus the other ethnicities. Co-immunoprecipitation analysis revealed a stronger DBP interaction with mVDR in FA compared to other ethnicities. Our data suggest that low DBP correlates with low mVDR in FA, whereas high DBP correlates with high mVDR in the other ethnicities. In conclusion, the strong interaction of DBP with mVDR in FA may implicate the potential role of DBP-mVDR crosstalk in aggressive thyroid cancer. Future research goals will be aimed at determining pathways involved in BDP-mVDR crosstalk in thyroid cancer health disparities. B. Mull, R. Davis, I. Munir, M.C. Perez, A.A. Simental, S. Khan, Differential expression of Vitamin D binding protein in thyroid cancer health disparities, Oncotarget 12(7) (2021) 596-607. Presentation: Monday, June 13, 2022 11:30 a.m. - 11:45 p.m.