VDR mRNA overexpression is associated with worse prognostic factors in papillary thyroid carcinoma

Abstract

The purpose of this study was to assess the relationship between vitamin D receptor gene (VDR) expression and prognostic factors in papillary thyroid cancer (PTC). mRNA sequencing and somatic mutation data from The Cancer Genome Atlas (TCGA) were analyzed. VDR mRNA expression was compared to clinicopathologic variables by linear regression. Tree-based classification was applied to find cutoff and patients were split into low and high VDR group. Logistic regression, Kaplan–Meier analysis, differentially expressed gene (DEG) test and pathway analysis were performed to assess the differences between two VDR groups. VDR mRNA expression was elevated in PTC than that in normal thyroid tissue. VDR expressions were high in classic and tall-cell variant PTC and lateral neck node metastasis was present. High VDR group was also associated with classic and tall cell subtype, AJCC stage IV and lower recurrence-free survival. DEG test reveals that 545 genes were upregulated in high VDR group. Thyroid cancer-related pathways were enriched in high VDR group in pathway analyses. VDR mRNA overexpression was correlated with worse prognostic factors such as subtypes of papillary thyroid carcinoma that are known to be worse prognosis, lateral neck node metastasis, advanced stage and recurrence-free survival.

Vitamin D Receptor Polymorphism and Cancer: An Update

“…The results of these studies also suggest that studying VDR polymorphisms in order to strengthen our understanding of the vitamin D pathway could provide additional evidence for its protective therapeutic role against cancer development (33,79). VDR polymorphisms might also serve as indicators for diagnosis, occurrence, and prognosis as well as survival in cancer (24,64,(75)(76)(77)(78)(83)(84)(85). There have been many epidemiological studies of breast, prostate and colorectal cancer, however, there are limited reports on the association of VDR polymorphism with lung, thyroid, oesophageal, ovarian, renal and hepatocellular carcinoma.…”

“…A casecontrol study including 426 patients with non-small cell lung cancer (NSCLC) and 445 controls from China studying VDR polymorphisms rs1544410 and rs731236 found a statistically significant relation between VDR polymorphism and reduction in NSCLC risk (82). Furthermore, the association of increased VDR mRNA expression with worse prognostic factors in papillary thyroid carcinoma suggests the role of VDR in thyroid cancer (83). Since vitamin D deficiency is associated with thyroid diseases and its metabolism is regulated by thyroid hormone, VDR polymorphism may play a role in pathogenesis and prognosis of thyroid cancer (84).…”

Expression based biomarkers and models to classify early and late-stage samples of Papillary Thyroid Carcinoma

“…On the basis of multidimensional data analysis, this study proposed the reclassification of thyroid cancers into molecular subtypes that better reflect the underlying molecular signaling pathways, which will further lead to better disease management [12]. Besides, several studies have also tried to reanalyze this data to understand the association of genomic features with survival and progression [13][14][15][16]. For instance, Chai et al have shown that the higher expression of BRAF is associated with high tumor aggressiveness regardless of the BRAF mutation status.…”

“…In literature, it has been shown that the methylation status of markers like RASSF1, DAPK1, and ESR1 has been significantly associated with thyroid cancer subtypes and early detection of thyroid cancer [18]. Furthermore, high expression of VDR has been observed to be associated with classic and tall cell subtype, stage IV, and low recurrence-free survival of thyroid cancer [13]. Moreover, previously, it has been shown that transforming growth factor, CDH1, COL1A1, CTNNA1, ITGA3, and FN1 were differentially expressed between benign and malignant nodules of thyroid cancer [19].…”

Influence of Interleukin-18 and Interleukin-17 Receptor A gene polymorphisms on the risk of thyroid cancer among Chinese Han population

“…TC led the fifth most common cancer in women in the United States [2], while the estimates of cancer incident cases and deaths were 143.9 thousand and 6500 respectively in China [3]. Although the exact pathophysiologic mechanisms of TC remained elusive, accumulating evidence indicated that the inter-individual genetic factors, especially the single nucleotide polymorphisms (SNPs) in tumor-associated genes took essential part in the genetic susceptibility to TC [4][5][6][7].…”