Role of vitamin D receptor and calcium sensing receptor in parathyroid cancer.

OBJECTIVES

Role of Vitamin D Receptor (VDR), Calcium Sensing Receptor (CaSR) and their associated long non-coding RNAs (lncRNAs) in Parathyroid Cancer (PC) development and PC diagnosis need to be explored. LncRNA SLC2A1-DT and SLC22A5-AS1 were dysregulated in previous microarray study. LncRNA SLC2A1-DT may target on VDR in prediction. Meanwhile, lncRNA SLC22A5-AS1was associated with CaSR.

METHODS

12 patients with PC and 43 patients with Parathyroid Adenoma (PA) were enrolled in this study. Fresh tissue samples were collected. Quantitative Real-Time Polymerase Chain Reaction (RT-qPCR) were used to assess the mRNA expression level of VDR and CaSR. In addition, protein level of VDR and CaSR were evaluated by Immunofluorescence (IF) detecting. Furthermore, expression level of lncRNA SLC2A1-DT, which may target on VDR in prediction, was validated by RT-qPCR in this study. Meanwhile, expression level of lncRNA SLC22A5-AS1, which was associated with CaSR in previous microarray study, was also detected by RT-qPCR.

RESULTS

Down-regulated mRNA expression levels of VDR (p = 0.003) and CaSR (p = 0.000) were detected in patients with PC. Consistent with the mRNA profile, protein expression levels for these two genes were also decreased in PC group in IF detection. In addition, association between VDR and CaSR were also confirmed in patients with hyperparathyroidism (p = 0.000). However, there was no significant difference in Area Under Curve (AUC) among VDR, CaSR and PTH in parathyroid cancer diagnosis. Meanwhile, there was no difference in lncRNA SLC2A1-DT and SLC22A5-AS1 expression levels in RT-qPCR validation. However, expression levels of lncRNA SLC2A1-DT (p = 0.004) and SLC22A5-AS1 (p = 0.002) were increased in PC patients with normal serum phosphorus. In patients with normal serum phosphorus, the AUC of SLC2A1-DT was 0.896 (p < 0.001). Similarly, the AUC of SLC22A5-AS1 was 0.920 (p < 0.001).

CONCLUSION

Decreased VDR and CaSR may play a role in parathyroid cancer. VDR and CaSR may have interaction in hyperparathyroidism. LncRNA SLC2A1-DT and SLC22A5-AS1 were dysregulated in PC patients with normal phosphorate. These lncRNAs could serve as potential biomarkers for PC patients with normal phosphorus.

LEVEL OF EVIDENCE: This diagnostic or monitoring test accurate? (Diagnosis). LEVEL 4: Case-control studies.