Background: Head and neck squamous cell carcinoma (HNSC) is one of the most common tumors worldwide. Nuclear transport factor 2 (NUTF2) plays a key role in cell death and immune processes. However, few reports have studied correlations between NUTF2 gene expression and the occurrence and development of HNSC.
Methods: The expression of NUTF2 was analyzed using publicly available databases, including the Cancer Genome Atlas and Human Protein Atlas and Gene Expression Omnibus (GEO) database, which was validated by RT-PCR. We evaluated the functions of NUTF2 with Kaplan–Meier curve, logistic regression were used to study the relationship between clinicopathological features and the expression of NUTF2. Cox regression analyses were used to identify the effects of NUTF2 expression on survival. Gene Ontology and Gene Set Enrichment Analysis were used to explore relevant biological pathways. The relationship between NUTF2 and tumor-infiltrating immune cells was investigated with on-line bioinformatic tools.
Results: NUTF2 was significantly upregulated in HNSC lesions and is associated with tumor size (P < 0.01). Increased expression of NUTF2 was linked to shorter overall and progress-free survival in HNSC. Cox regression analyses revealed that NUTF2  is an independent prognostic factor in HNSC. GSEA analysis demonstrated that NUTF2 negatively regulates several immune pathways. NUTF2 was correlated with the infiltrating levels of B cells and CD8+ T cells and was negatively correlated with diverse immune marker sets in HNSC.
Conclusion: NUTF2 is highly expressed in HNSC and correlates with poor prognosis. Correlation with immune functions suggests that NUTF2 may serve as a biomarker and therapeutic target for HNSC.
Keywords: NUTF2, head and neck squamous cell carcinoma, immune infiltration, prognostic biomarker