TP53 As A Early Recurrence-Linked Biomarker In Tongue Squamous Cell Carcinoma: A Proteomic And Bioinformatic Study

Abstract

Tongue squamous cell carcinoma (TSCC) is characterized by high recurrence rates and poor prognosis, yet the underlying molecular mechanisms remain incompletely defined. This study investigates the role of TP53 in TSCC recurrence using integrative proteomic and bioinformatic approaches. Unpublished LC-MS/MS data of our research revealed significant upregulation of TP53 in early recurrence-positive samples compared to non-recurrent cases. To contextualize this finding, TP53 was compared to 16 recurrence-associated genes (e.g., FOXM1,OCT4, SNAI1, BRCA1/2, BCL2, EGFR, ALDH1A1, CD44, MYC, PTEN, SOX2, TWIST1, NANOG, and ABCB1) through BLASTp alignment and phylogenetic analysis. Homology modeling of TP53 was conducted via SWISS-MODEL using the top-scoring PDB template, and model quality was validated by Ramachandran plot analysis. Molecular docking using AutoDock Vina showed favourable binding of carboplatin (–3.6 kcal/mol) and 5-fluorouracil (–3.4 kcal/mol) to the TP53 core domain, with interactions involving key binding residues. Protein–protein interaction analysis via STRING identified TP53 hub connections to MDM2, CDKN1A, and DNA damage regulators. Functional enrichment using DAVID highlighted TP53 involvement in apoptosis, cell cycle arrest, and the p53 signaling pathway. Collectively, these findings support TP53 as a key molecular player in TSCC recurrence and a potential target for therapeutic intervention.