FAM117B and ZDHHC21 as Shared Targets in Periodontitis and Oropharyngeal Cancer: Cephaeline and Sanguinarine as Potential Therapeutics

Introduction: Periodontitis (PD) and oropharyngeal cancer (OPC) are distinct dis-eases, but emerging evidence suggests potential molecular and immunological intersections, particularly in chronic inflammation influencing carcinogenic processes. Methods: Transcriptomic analysis combining bulk RNA-seq and single-cell RNA-seq data (PD: GSE10334; OPC: GSE3292) was performed. Co-expression networks were constructed, and feature selection was conducted using Random Forest and LASSO regression. Survival analysis, ROC validation, immune profiling, and molecular docking were used for further val-idation. Functional assays, including CCK-8, colony formation, and wound healing assays, were performed to evaluate the effects of overexpression of FAM117B and ZDHHC21 in FaDu cells. Results: Transcriptome analysis revealed 3,450 DEGs in PD and 447 in OPC. Twelve shared genes, including FAM117B and ZDHHC21, were identified. These genes showed significant survival benefits (HR = 0.71, p lt; 0.05) and strong diagnostic performance (FAM117B AUC = 0.87 in PD, 0.89 in OPC). Immune profiling showed correlations with macrophages, NK cells, dendritic cells, and plasma cells. Functional assays demonstrated that overexpression of FAM117B and ZDHHC21 significantly inhibited cell proliferation, colony formation, and mi-gration. Cephaeline and Sanguinarine showed strong binding affinities for FAM117B and ZDHHC21, respectively, with MD simulations confirming their potential as computational predicted binders. Discussion: The shared molecular signatures between PD and OPC suggest that chronic peri-odontal inflammation may foster an oncogenic microenvironment conducive to OPC progres-sion. FAM117B and ZDHHC21 appear central in this convergence, linking immune dysregu-lation with tumor biology. The therapeutic potential of Cephaeline and Sanguinarine could bridge insights with clinical applications. Conclusion: FAM117B and ZDHHC21 are key molecular targets linking PD and OPC. Ceph-aeline and Sanguinarine are promising therapeutic agents that offer novel insights into the PD–OPC molecular convergence, providing a basis for further experimental validation and clinical translation.