Multi-Omics Mendelian Randomization Identifies Drug Targets For Oscc

Although significant progress has been made in the treatment of oral squamous cell carcinoma (OSCC), a substantial subset of patients still respond poorly to existing therapies, partly due to the lack of effective therapeutic targets. We performed summary-data-based Mendelian randomization (SMR) analysis using expression quantitative trait loci (eQTL) (sample size 31,684) and DNA methylation quantitative trait loci (mQTL) data (sample size 1,980). OSCC Genome-wide association studies (GWAS) data included two independent cohorts (4,151 samples with 1,223 cases and 3,464 samples with 1,135 cases). Colocalization analysis was conducted to identify shared causal variants between OSCC risk and gene expression. Drug prediction and molecular docking were performed to validate therapeutic potential. 12 drug targets (BTNL2, CLIC1, HCP5, HLA-B, HLA-DQB1, HLA-DQB2, NOTCH1, POU5F1, PRKD1, PSORS1C1, SEPP1, TSBP1-AS1) showed significant SMR associations (p<0.05) with colocalization support. These genes demonstrate dual associations with immune function and cancer pathogenesis, based on their targeting by both immunotherapeutic and antineoplastic agents. Molecular docking revealed strong binding affinities between identified targets and existing drug compounds (average docking score < -9.0 kcal/mol). We identified 12 high-confidence drug targets for OSCC with both genetic and structural validation. These targets may improve precision therapy development and prioritize OSCC drug development and save on drug development costs.