Abstract
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.
Highlights
Thyroid cancer is one of the most prevalent endocrine cancers [1,2,3,4]
We evaluated the D binding protein (DBP) staining intensity in thyroid cancer tissues derived from Filipino Americans (FA) (FPTC) and European Americans www.oncotarget.com (EA) (EATC)
Negative (0, n = 90) to weak (1+, n = 10) staining patterns were observed throughout the FATC (Figure 1F and 1H), Some of them showed very weak to total loss of DBP expression (Supplementary Figure 2B, 2D, 2F, 2H, 2J, 2L, 2N and 2P), and consulted the patient chart for demographic data and cancer staging
Summary
Thyroid cancer is one of the most prevalent endocrine cancers [1,2,3,4]. An epidemic of thyroid cancer (TC) in California was reported by the California-based Cancer Prevention Institute [2, 5,6,7,8,9]. It is believed that there is an actual increase in thyroid cancer incidence due to changes in risk factors [17,18,19,20,21], the exact mechanism of this steady increase remains unknown. According to the analysis of ethnicity and geographical residence, variations in thyroid cancer incidence may be attributed www.oncotarget.com to local environmental influences and genetic/biological alterations [10, 22, 23]. We identified a highly polymorphic protein, called vitamin D binding protein (DBP) that could play an important role in thyroid cancer progression in ethnically predisposed group. Because of its highly polymorphic nature in humans [24,25,26,27,28], a structural/functional defect of DBP gene could contribute to thyroid cancer development and malignant transformation
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