# Identification of Basement Membrane-Related Biomarkers in the Progression of Cutaneous Squamous Cell Carcinoma

## TL;DR

This study identifies genes related to basement membrane changes in skin cancer progression, offering new insights and potential treatment targets.

## Contribution

The study identifies novel basement membrane-related genes that distinguish invasive skin cancer from precursor conditions and suggests potential therapeutic targets.

## Key findings

- Six to nine central hub basement membrane-related genes were identified for each stage of cSCC progression with high AUC values.
- Genes like ITGB1, LAMA3, and FN1 were upregulated in keratinocytes and fibroblasts during cSCC progression compared to AK or BD.
- The findings suggest these genes play a role in basement membrane breaching and cancer invasion.

## Abstract

Basement membrane (BM) breaching is a critical hallmark of cutaneous squamous cell carcinoma (cSCC) invasion. This study aimed to identify novel BM-related genes (BMRGs) to effectively distinguish invasive cSCC from actinic keratosis (AK) and Bowen’s disease (BD), and to identify potential therapeutic targets. Single-cell RNA sequencing was used for BMRGs identification within keratinocytes and fibroblasts clusters. Protein–protein interaction network analysis and Lasso regression were performed for hub BMRGs screening, together with nomogram model construction and validation. In this study, 6–9 central hub BMRGs were identified for each stage during cSCC progression with a good AUC value (>0.8). In keratinocytes, BMRGs such as integrins (ITGB1, ITGA3, ITGA6), laminins (LAMA3, LAMC1), CD44, and FN1 were upregulated in cSCC compared to AK or BD (adjusted p < 0.05); in fibroblasts, BMRGs including ITGB1, ITGAV, LUM, BGN, SDC1, and FN1 were upregulated in cSCC (adjusted p < 0.05), suggesting their collective role in BM breaching and invasion, as well as a higher risk of BD. This study provides novel biological insights into the differentiation of progression pathways from AK or BD to cSCC, as well as potential targets for therapeutic intervention.