Investigating differential claudin expression and interactome in oral squamous cell carcinoma

<p dir="ltr">Oral squamous cell carcinoma (OSCC) is a highly aggressive cancer, with poor prognosis due to frequent recurrence and metastasis. Claudins (CLDNs), a family of transmembrane proteins involved in tight junction formation, cellular signaling, play vital roles in cancer progression, including OSCC.</p><p dir="ltr">This study utilizes bioinformatics, molecular docking, and molecular dynamics (MD) simulation to assess CLDNs as therapeutic targets in OSCC. Differential expression analysis of GEO dataset revealed upregulation of CLDN1 and downregulation of CLDN4, CLDN7, CLDN17. Gene Ontology linked CLDNs to tight junction and antigen processing, while PPI networks highlighted EGFR, CDH1, and AKT1 as key CLDN1 interactors. Genetic alterations via cBioportal and UALCAN validated CLDN1 and CLDN17 significance, reinforcing CLDN1 as a clinically relevant target due to its role in proliferation, migration, and poor prognosis.</p><p dir="ltr">Virtual screening of 1,055 molecules against CLDN1 identified anticancer agents 32 (–7.4 kcal/mol) and 31 (–7.0 kcal/mol) with the strongest docking scores. Whereas MD simulations revealed agent 31 as the most stable inhibitor (binding free energy –38.698 kcal/mol).</p><p dir="ltr">Overall, these findings suggest CLDN1 may serve as both a promising biomarker and therapeutic target in OSCC, with anticancer agent 31 offering potential for future drug development and preclinical validation.</p>