Diagnostic Value of VDR in Bone Metastasis and Prognosis of Patients with Breast Cancer and Expression Correlation between Vitamin D Receptor and Hairless Protein

Abstract

Background: Breast cancer is more likely to metastasize to the bone. Previous researches have revealed that the vitamin D receptor (VDR) contributes to breast cancer progression and bone metastasis in mouse and human breast cells, and hairless (Hr) protein interacts with VDR in the mammalian hair cycle. This study aimed to explore the expression of VDR/Hr in breast cancer, and the correlation between VDR/Hr and prognosis, bone metastasis, and metastasis-related prognosis.

Methods: The expression of VDR and Hr was analyzed on 119 breast cancer tissues and corresponding normal breast tissue from each of the breast cancer samples by immunohistochemistry staining, and the databases were supplemented as well.

Results: The expression of the VDR protein was significantly decreased in breast cancer patients (p < 0.05), inversely, the UALCAN (p = 0.000) and GEPIA (p > 0.05) databases showed that the VDR mRNA expression tended to be higher in tumor tissues. The Hr protein was expressed at a low level within breast cancer specimens (p < 0.05), which was in agreement with the level of Hr mRNA in UALCAN (p = 0.005) and GEPIA (p > 0.05). The protein levels of VDR and Hr were positively correlated (p > 0.05), while the mRNA levels suggested a close relationship with GEPIA (p < 0.05). Low expression of Hr protein displayed a tendency for longer overall survival (OS) and recurrence-free survival (RFS), and its mRNA data also revealed the same trend in the Kaplan-Meier dataset (both p > 0.05). However, VDR protein and mRNA with low expression had markedly shorter OS and RFS (both p < 0.05). The downregulation of VDR protein was significantly associated with an advanced stage (p < 0.05). Low VDR protein was an independent risk factor for poor prognosis (p < 0.05) and was negatively correlated with bone metastasis (p < 0.05). VDR protein and mRNA levels were both downregulated in breast cancer with bone metastasis (both p < 0.05). The area under ROC curve (AUC) for VDR protein expression to identify patients with bone metastasis was 0.661 (p < 0.05) and the AUC for VDR level to predict 1-year, 3-year, and 5-year OS was 0.621, 0.664, and 0.805 in patients with bone metastasis, respectively (p < 0.05). VDR with low expression accelerated bone metastasis and metastasis-related poor survival (both p < 0.05).

Conclusion: VDR expression is a notable prognostic factor in primary breast cancer patients for predicting bone metastases and unfavorable clinical outcome.

Keywords: Bone metastasis; Breast cancer; Hairless; Prognosis; Vitamin D receptor.