Revealing CASQ1 as a potential target for Oral Squamous Cell Carcinoma through gene expression and functional analysis: An In Silico Approach

Oral squamous cell carcinoma (OSCC) is a prevalent and aggressive malignancy with limited therapeutic options and high mortality, largely due to late diagnosis and treatment resistance. This study employed an integrative in silico pharmacology strategy to identify novel druggable targets in OSCC. Nineteen GEO transcriptomic datasets (435 samples) were analyzed, yielding 580 significantly overexpressed genes (logFC > 2.5). Network and enrichment analyses highlighted CASQ1 (calsequestrin 1), a calcium-binding protein, as a hub gene within a sarcomeric cluster implicated in epithelial–mesenchymal transition and OSCC progression. To explore its therapeutic potential, molecular docking and 100 ns molecular dynamics (MD) simulations were performed with standard chemotherapeutics, fluorouracil and docetaxel. Fluorouracil exhibited strong binding affinity (–7.225 kcal/mol) and stable conformational dynamics with CASQ1, while docetaxel showed more flexible but persistent binding. These results suggest that CASQ1 is a previously unrecognized drug-interactable target in OSCC and may represent a novel pharmacological vulnerability. Overall, this study demonstrates how integrative computational approaches, spanning gene expression profiling to drug–target interaction modeling, can accelerate target discovery and inform therapeutic strategies in oncology.