Transcriptomic analysis of genes associated with vitamin D receptor signalling reveals differences between skin...

Area of Science:

• Dermatology
• Molecular Biology
• Oncology

Background:

• The vitamin D receptor (VDR) heterodimerizes with the retinoid X receptor-alpha (RXRα) to regulate gene expression.
• This VDR/RXRα complex plays a role in cellular processes relevant to skin cancer development.

Purpose of the Study:

• To compare mRNA expression of the VDR/RXRα heterodimer and associated genes in non-melanoma skin cancers (basal cell carcinoma, squamous cell carcinoma) and melanocytic lesions (intradermal nevi, melanoma) versus control skin.
• To identify potential biomarkers and therapeutic targets within the VDR/RXRα pathway in skin lesions.

Main Methods:

• Nanostring® gene expression analysis was performed on mRNA from 46 paraffin-embedded skin samples.
• Samples included basal cell carcinomas (BCC), squamous cell carcinomas (SCC), intradermal nevi (IN), melanomas (MM), and control skin.
• Expression levels of VDR, RXRα, and 22 other correlated genes were quantified.

Main Results:

• VDR and RXRα mRNA levels were significantly lower in all tested skin lesions (BCC, SCC, IN, MM) compared to control skin.
• NCOR2 was upregulated in BCC and SCC, while RXRγ was higher in MM and IN compared to controls.
• Distinct gene expression patterns were observed between non-melanocytic cancers (BCC/SCC) and melanocytic lesions (IN/MM), with TP53, FOXO3, and MED1 differing between BCC and SCC, and AhR differentiating melanoma from nevi.

Conclusions:

• The VDR/RXRα pathway is dysregulated in various skin lesions, with reduced VDR and RXRα expression being a common feature.
• Specific gene expression profiles highlight differences between non-melanocytic and melanocytic skin tumors.
• Understanding the VDR/RXRα pathway's role in skin cancer may inform future prevention and treatment strategies, particularly for non-melanocytic tumors.