Evolutionary Action Score of TP53 Identifies High-Risk Mutations Associated with Decreased Survival and Increased Distant Metastases in Head and Neck Cancer

摘要: TP53 is the most frequently altered gene in head and neck squamous cell carcinoma (HNSCC) with mutations occurring over two third of cases, but prognostic significance these remains elusive. In current study, we evaluated a novel computational approach termed Evolutionary Action (EAp53) to stratify patients tumors harboring as high or low risk, validated this system both vivo vitro models. Patients risk had poorest survival outcomes shortest time development distant metastases. Tumor cells expressing were more invasive tumorigenic they exhibited higher incidence lung We also documented an association between presence decreased expression target genes, highlighting key cellular pathways that are likely be dysregulated by subset p53 which confer particularly aggressive tumor behavior. Overall, our work EAp53 tool may useful clinical prognosis mutations.