Nuclear Transporting Factor 2 as a Novel Biomarker of Head and Neck Squamous Cell Carcinoma and Associated with T/B Cell Receptor Signaling Pathway

Biomed Res Int. 2022 Feb 4:2022:2885323. doi: 10.1155/2022/2885323. eCollection 2022.

Abstract

Objective: This study is aimed at exploring the role of nuclear transporting factor 2 (NUTF2) in head and neck squamous cell carcinoma (HNSCC) based on The Cancer Genome Atlas (TCGA) database.

Methods: We obtained 528 HNSCC patients' clinical data from TCGA and performed expression level analysis of NUTF2. Gene Sets Enrichment Analysis (GSEA) was conducted to identify NUTF2-associated regulatory mechanisms in HNSCC. In addition, several other tools were used to enrich the regulatory network.

Results: We found that NUTF2 was significantly upregulated (P < 0.001) in HNSCC. We then observed that higher NUTF2 is associated with poorer overall survival and disease-free survival. Further, by using Cox analyses, we determined high NUTF2 as an independent risk factor of predicting poorer overall survival. Tumor immune infiltration analysis revealed a significantly negative correlation between NUTF2 expression and the level of tumor infiltrated CD8+ T cell and B cell, suggesting that NUTF2 may be involved in the immune regulation of HNSCC. Gene sets related to T/B cell receptor signaling pathways were differentially enriched based on the NUTF2 expression phenotype. KEGG pathways were used to show that NUTF2 may affect proliferation, differentiation, and immune response of T/B cell through regulating PI3K/AKT, NFκB, MAPK, and Calcium signaling pathways.

Conclusion: NUTF2 might be a valuable biomarker for HNSCC and correlated with T/B cell receptor signaling pathway.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Databases, Genetic
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • Humans
  • Male
  • Middle Aged
  • Nucleocytoplasmic Transport Proteins / genetics*
  • Pregnancy Proteins / genetics*
  • Receptors, Antigen, B-Cell / metabolism*
  • Receptors, Antigen, T-Cell / metabolism*
  • Signal Transduction
  • Squamous Cell Carcinoma of Head and Neck / genetics*
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • NUTF2 protein, human
  • Nucleocytoplasmic Transport Proteins
  • Pregnancy Proteins
  • Receptors, Antigen, B-Cell
  • Receptors, Antigen, T-Cell