VDR is a potential prognostic biomarker and positively correlated with immune infiltration - a comprehensive pan-cancer analysis with experimental verification

Sep 21, 2026

The vitamin D receptor (VDR) mediates diverse effects of 1,25-dihydroxyvitamin D3, yet its clinical significance in human cancers remains unresolved. Relationships among VDR expression, prognosis, immune infiltration, tumor microenvironment, and gene set enrichment were assessed across 33 cancer types using multiple public databases and R. Experimental validation focused on papillary thyroid cancer (PTC), linking altered VDR levels with immune- and stromal-enriched tumor microenvironments, and showing inhibited PTC proliferation and migration.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages24

Reading Time1 h 0 min

AccessFree to download

Introduction

Vitamin D and VDR background

Clinical controversy and prior evidence

Rationale for pan-cancer analysis

Bioscience Reports (2024) 44 BSR20231845 [https://doi.org/10.1042/BSR20231845](https://doi.org/10.1042/BSR20231845) Research Article VDR is a potential prognostic biomarker and positively correlated with immune inﬁltration: a comprehensive pan-cancer analysis with experimental veriﬁcation Xuedi Xia, Feng Xu, Dexing Dai, An Xiong, Ruoman Sun, Yali Ling, Lei Qiu, Rui Wang, Ya Ding, Miaoying Lin, Haibo Li and Zhongjian Xie National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha 410011, Hunan, China Correspondence: Zhongjian Xie ([zhongjian.xie@csu.edu.cn](zhongjian.xie@csu.edu.cn)) Received: 30 October 2023 Revised: 08 March 2024 Accepted: 17 April 2024 Accepted Manuscript online: 19 April 2024 Version of Record published: 30 April 2024 The vitamin D receptor (VDR) is a transcription factor that mediates a variety of biological functions of 1,25-dihydroxyvitamin D3. Although there is growing evidence of cytological and animal studies supporting the suppressive role of VDR in cancers, the conclusion is still controversial in human cancers and no systematic pan-cancer analysis of VDR is available. We explored the relationships between VDR expression and prognosis, immune infiltration, tumor microenvironment, or gene set enrichment analysis (GSEA) in 33 types of human cancers based on multiple public databases and R software. Meanwhile, the expression and role of VDR were experimentally validated in papillary thyroid cancer (PTC) . VDR expression decreased in 8 types and increased in 12 types of cancer compared with normal tissues. Increased expression of VDR was associated with either good or poor prognosis in 13 cancer types. VDR expression was positively correlated with the infiltration of cancer-associated fibroblasts, macrophages, or neutrophils in 20, 12, and 10 cancer types respectively and this correlation was experimentally validated in PTC. Increased VDR expression was associated with increased percentage of stromal or immune components in tumor microenvironment (TME) in 24 cancer types. VDR positively and negatively correlated genes were enriched in immune cell function and energy metabolism pathways, respectively, in the top 9 highly lethal tumors. Additionally, VDR expression was increased in PTC and inhibited cell proliferation and migration. In conclusion, VDR is a potential prognostic biomarker and positively correlated with immune infiltration as well as stromal or immune components in TME in multiple human cancers. Introduction Vitamin D is primarily recognized for its role in regulating calcium homeostasis and bone health. In recent years, increasing number of studies have revealed that vitamin D has a wide range of potential extra-skeletal effects [1–4], such as anti-cancer effects [5] . VDR mediates the biological actions of 1,25-dihydroxyvitamin D3 . VDR is widely expressed in human tissues such as intestine, kidney, heart, brain, skin, prostate, and ovary [6] . Studies have shown that VDR inhibits tumor progression by suppressing cell stemness in pancreatic cancer and colitis-associated tumorigenesis in colon cancer[7,8] . Knockout ofVDR increases carcinogen-induced mammary hyperplasia and tumor progression in the epidermis and lymphoid tissue in mice [9] . These observations suggest that VDR might serve as a tumor suppressor. © 2024 The Author(s) . This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution 1 License 4 .0 (CC BY) . Bioscience Reports (2024) 44 BSR20231845 [https://doi.org/10.1042/BSR20231845](https://doi.org/10.1042/BSR20231845) Although the results of cytological studies and animal experiments are encouraging [10–12], the results of clinical studies are controve

FAQs

What question does the study address about VDR in cancer?

It evaluates whether VDR can serve as a prognostic biomarker and how VDR expression relates to immune infiltration and the tumor microenvironment across many cancer types.

How was VDR expression associated with cancer outcomes?

VDR expression showed decreased levels in 8 cancer types and increased levels in 12 cancer types, and higher expression was linked to either good or poor prognosis depending on the cancer type.

What experimental validation was performed and what were the key functional findings?

The study experimentally validated immune-related correlations and VDR-related roles in papillary thyroid cancer (PTC); increased VDR in PTC was associated with inhibited cell proliferation and migration.

Sep 21, 2026

Uploaded by Emma Wilson