Differential expression of Vitamin D binding protein in thyroid cancer health disparities
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Brittany Mull1, Ryan Davis2,3, Iqbal Munir4, Mia C. Perez5, Alfred A. Simental6 and Salma Khan2,3,6,7
1 Harbor UCLA Medical Center, Torrance, CA 90502, USA
2 Division of Biochemistry, Loma Linda, CA 92350, USA
3 Center for Health Disparities & Molecular Medicine, Loma Linda, CA 92350, USA
4 Riverside University Health System, Moreno Valley, CA 92555, USA
5 Department of Pathology & Human Anatomy, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA
6 Department of Otolaryngology, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA
7 Department of Internal Medicine, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA
Keywords: DBP; thyroid cancer; health disparities
Received: November 16, 2020 Accepted: March 05, 2021 Published: March 30, 2021
Thyroid cancer incidence, recurrence, and death rates are higher among Filipino Americans than European Americans. We propose that vitamin D binding protein (DBP) with multifunctionality with ethnic variability plays a key role within different ethnicities. In this study, we determined the correlation between differential DBP expression in tumor tissues and cancer staging in Filipino Americans versus European Americans. We assayed DBP expression by immunohistochemistry and analyzed the data with confocal microscopy on 200 thyroid cancer archival tissue samples obtained from both ethnicities. DBP-stable knockdown/gain-in-function assays were done by using DBP-shRNA/DBP-cDNA-expression in vitro. The majority of Filipino Americans presented with advanced tumor staging. In contrast, European Americans showed early staging and very few advanced tumors. A significantly low to no DBP staining was detected and correlated to the advanced staging in Filipino Americans. On the contrary, in the tumor tissues derived from European Americans, moderate to strong DBP staining was detected and correlated to early staging. When downregulation of the DBP gene in papillary thyroid cancer (PTC) cell lines was observed, tumor proliferation and migration were enhanced. On the other hand, the upregulation of the DBP gene decreased cell proliferation and migration in PTC cells. In conclusion, we determined a differential expression of an essential biological molecule (DBP) is linked to cancer staging in thyroid cancer health disparities in two ethnicities. Loss-of-DBP/gain-in-DBP-function influenced tumor progression. A future study is underway to determine the DBP regulation and its downstream pathways to elucidate strategies to eliminate the observed thyroid cancer health disparities.
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