TP53-Associated Ion Channel Genes Serve as Prognostic Predictor and Therapeutic Targets in Head and Neck Squamous Cell Carcinoma

Abstract

TP53 mutations are the most occurred mutation in HNSCC which might affect the ion channel genes. We aim to investigate the ion channel gene alteration under TP53 mutation and their prognostic implication. The overall mutation status of HNSCC were explored. By screening the TP53-associated ion channel genes (TICGs), an ion channel prognostic signature (ICPS) was established through a series of machine learning algorithms. The ICPS was then evaluated and its clinical significance was explored. 82 TICGs differentially expressed between TP53WT and TP53MUT were screened. Using univariate regression analysis and LASSO regression analysis and multivariate regression analysis, an ICPS containing 7 ion channel genes was established. A series of evaluation was carried out which proved the predictive ability of ICPS. Functional analysis of ICPS revealed that cancer-related pathways were enriched in high-risk group. Next, for clinical application, a nomogram was constructed based on ICPS and other independent clinicopathological factors. TP53 mutation status strongly affects the expression of ion channel genes. The ICPM we have identified is a strong indicator for HNSCC prognosis and could help with patient stratification as well as identification of novel drug targets.