Shared patterns of dysregulated gene expression across squamous cell carcinomas unveil predictors for prognosis and drug sensitivity.

Despite extensive multi-omics studies on squamous cell carcinomas (SCCs) across different organs, the shared transcriptional regulatory mechanisms that driving SCC remain unclear. This study systematically identified common and distinct transcriptomic alterations in SCCs, highlighting key genes and pathways with prognostic and therapeutic relevance. By integrating large-scale gene expression data from SCC tumors and adjacent normal tissues, we revealed dysregulated gene expression patterns (DGEPs) and quantified their similarity across SCCs through correlation and regression analyses. Gene co-expression network analysis identified SCC-associated modules and hub genes, whose biological and clinical significance was further explored through subtype analysis and prognostic modeling. Our findings show that SCCs from the head and neck, esophagus, and cervix share highly similar DGEPs and regulatory networks, whereas lung and skin SCCs exhibit more distinct molecular characteristics. Key processes such as epithelial-mesenchymal transition, extracellular matrix remodeling, and immune-related pathways were strongly linked to SCC prognosis. Moreover, a six-gene prognostic signature (COL1A1, MMP1, SERPINE1, KRT6A, IGF2BP3, and SPP1) demonstrated robust predictive power for clinical outcomes and therapy response. These findings provide insights into SCC progression and potential therapeutic targets.