AUTHOR=Xuan Guangxu , Zhang Xin , Zhang Min , Yu Minghang , Zhou Yujie , He Xiaosong , Hu Xiaopeng , Wang Xi , Liu Liangfa 

TITLE=NTF2 Upregulation in HNSCC: a Predictive Marker and Potential Therapeutic Target Associated With Immune Infiltration

JOURNAL=Frontiers in Oncology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.783919

DOI=10.3389/fonc.2022.783919

ISSN=2234-943X

ABSTRACT=Background: Head and neck squamous cell carcinoma (HNSCC) is a type of malignant tumor with an increasing incidence worldwide and a meager 5-year survival rate. It is known that nuclear transporter factor 2 (NUTF2) transports related proteins into the nucleus physiologically. However, the role of NUTF2 in HNSCC remains unclear.
Methods: In this study, RNA-Seq data of HNSCC samples with corresponding clinical information were obtained from The Cancer Genome Atlas (TCGA) database. In addition, other expression profiling data were downloaded from the Gene Expression Omnibus (GEO) database. The differential expressions of NUTF2, along with the overall survival (OS) rates were identified and analyzed. Then, the clinical features and expression levels of NUTF2 were utilized to develop a prognostic model. The study also utilized the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) methods to determine the related pathways of NUTF2. Furthermore, the Tumor Immune Estimation Resource (TIMER) database was referenced to discover the immune correlates of NUTF2. In this research investigation, RT-qPCR, Western Blotting, Cell Counting Kit-8 (CCK-8) assay, wound-healing assay, and immunohistochemical (IHC) staining methods were adopted to perform experimental verifications.
Results: This study’s results confirmed that the NUTF2 expressions were significantly increased in HNSCC tissue when compared with normal tissue. In addition, the high expression levels of NUTF2 were found to be associated with poor prognoses, which was confirmed via the IHC validations. The results of this study’s functional enrichment analysis showed that the NUTF2 was associated with epithelial cell growth, skin differentiation, keratosis, and estrogen metabolism. Furthermore, the expressions of NUTF2 were determined to be negatively involved with immune infiltrations and correlated with immune checkpoint blockade (ICB) responses following various ICB therapy strategies. The results of the CCK-8 assay and wound-healing assay confirmed the NUTF2’s promoting effects on the proliferation and migration of tumor cells.
Conclusions: This study defined a novel prognostic model associated with the expressions of NUTF2, which was shown to be independently related to the OS of HNSCC. It was concluded in this study that NUTF2 may be a potential diagnostic and prognostic biomarker for HNSCC.