IVNS1ABP Expression Associates with HPV Status and TP53 Mutation in Head and Neck Squamous Cell Carcinoma: A TCGA-based Analysis

Abstract

Head and neck squamous cell carcinoma (HNSC) is a heterogeneous malignancy in which molecular biomarkers may aid tumor detection and clinically relevant subgrouping, including by human papillomavirus (HPV) status. Influenza virus NS1A binding protein (IVNS1ABP; NS1-BP) encodes a Kelch family protein involved in RNA processing and proteostasis-related pathways and has been implicated by human genetics in early-onset neuropathy syndromes.

We performed an in silico analysis of IVNS1ABP in the TCGA-HNSC cohort using the UALCAN and TIMER3 platforms. IVNS1ABP expression was significantly higher in HNSC tumors (n = 520) than in normal tissues (n = 44) and remained elevated across stages and grades. HPV-stratified analyses were definition-dependent: readcount-based stratification showed higher expression in HPV− than HPV+ tumors (p = 9.53×10^{- 9}), whereas p16/ISH-based grouping showed no significant difference. IVNS1ABP expression was higher in TP53-mutant tumors than in TP53-nonmutant tumors (p = 3.43×10^{- 6}) but did not correlate with TP53 mRNA levels. Overall survival was not significant in UALCAN, while TIMER3 stage-adjusted Cox analysis revealed a significant association in HPV+ disease (HR = 1.861, p = 0.015) but not in HPV− disease.

These findings indicate that IVNS1ABP is a tumor- and context-associated expression marker in HNSC, with potential relevance to HPV-stratified risk biology and future diagnostic or translational applications.