Abstract
Skin cutaneous melanoma (SKCM) and squamous cell carcinoma (SCC) are two prevalent forms of skin cancer, both characterized by extensive remodeling of the extracellular matrix (ECM), which facilitates tumor progression and metastasis. To investigate ECM-related gene expression alterations in SCC and assess their diagnostic and prognostic relevance in SKCM by integrating transcriptomic data with clinical outcomes. RNA-sequencing data from NCBI Gene Expression Omnibus (GEO) were analyzed to identify differentially expressed genes in SCC. Key findings were validated in The Cancer Genome Atlas (TCGA) SKCM dataset. Functional enrichment and protein-protein interaction (PPI) analyses were conducted to identify ECM-related pathways and hub genes. Matrix metalloproteinases MMP7, MMP11, and MMP14 were significantly upregulated in SCC and showed elevated expression in primary SKCM tumors, confirmed by RT-qPCR analysis. Functional enrichment revealed dysregulation of ECM-receptor interaction and IL-17 signaling pathways. PPI analysis identified MMP14 as central hub interacting with TIMPs, CD44, and FURIN. Kaplan-Meier survival analysis showed that elevated MMP11 and MMP14 expression correlated with worse overall survival. ROC curve analysis confirmed their strong diagnostic value, with MMP14 achieving an AUC of 0.955. MMP7, MMP11, and MMP14 play key roles in skin cancer progression. They show strong potential as diagnostic and prognostic biomarkers and may serve as therapeutic targets in SCC and SKCM.