Dual role of Cathepsin S in cutaneous melanoma: insights from mendelian randomization and bioinformatics analysis

作者：Linsa Zhou, Qiang Zhou, Qian Guo, Lai Peng, Chen Rui, Wanqing Li, Xuemei Chen, Yue Zhuo, Xiaoping Zhong, Sen Lin · 发表于：BMC Cancer · 年份：2025 · DOI：10.1186/s12885-025-13481-w · 被引用次数：12 · 研究领域：Ferroptosis and cancer prognosis、Inflammasome and immune disorders、Protease and Inhibitor Mechanisms

BACKGROUND: Cutaneous melanoma (CM) is strongly associated with ultraviolet (UV) radiation, which contributes to the transformation of melanocytes into melanoma by inducing specific DNA damage. Here, we investigated the causal relationship between CM and genes related to sun-damaged skin, exploring specific target genes through various bioinformatics analyses. METHODS: The Gene Expression Omnibus (GEO) database was used to obtain differential genes for CM and normal skin, and the Genome-Wide Association Studies (GWAS) analysis offered summary-level melanoma data for CM. Mendelian randomization (MR) analyses were used to examine the correlated linkage between CM and sun-exposed skin genes. The MR studies were conducted mainly using Inverse Variance Weighting (IVW), MR-Egger, Weighted Median, simple and weighted patterns to predict the correlation between sun-exposed skin and CM. Finally, the role of target genes in CM was revealed by pan-cancer analysis, expression and immune-infiltration evaluations, immuno-checking targeting analysis, immunotherapy response analysis, survival analysis, and protein-protein interactions (PPI) network and enrichment analyses. RESULT: Using matrix data from the GSE15605, GSE46517, and GSE111452 datasets, bioinformatics analysis revealed 232 differentially expressed genes (DEGs) between CM and typical tissues. MR analysis indicated that only CTSS has a deleterious effect linking skin exposure to sunlight and CM. Analysis of CTSS expression in tum...