AUTHOR=Xu Chengzhi , Zhang Yunbin , Shen Yupeng , Shi Yong , Zhang Ming , Zhou Liang 

TITLE=Integrated Analysis Reveals ENDOU as a Biomarker in Head and Neck Squamous Cell Carcinoma Progression

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.522332

DOI=10.3389/fonc.2020.522332

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>Head and neck squamous cell carcinoma (HNSCC) is a leading cancer with high morbidity and mortality worldwide. The aim is to identify genes with clinical significance by integrated bioinformatics analysis and investigate their function in HNSCC.</p></sec><sec><title>Methods</title><p>We downloaded and analyzed two gene expression datasets of GSE6631 and GSE107591 to screen differentially expressed genes (DEGs) in HNSCC. Common DEGs were functionally analyzed by Gene ontology and KEGG pathway enrichment analysis. Protein-protein interaction (PPI) network was constructed with STRING database and Cytoscape. <italic>ENDOU</italic> was overexpressed in FaDu and Cal-27 cell lines, and cell proliferation and migration capability were evaluated with MTT, scratch and transwell assay. The prognostic performance of ENDOU and expression correlation with tumor infiltrates in HNSCC were validated with TCGA HNSCC datasets.</p></sec><sec><title>Results</title><p>Ninety-eight genes shared common differential expression in both datasets, with core functions like extracellular matrix organization significantly enriched. 15 genes showed prognostic significance, and <italic>COBL</italic> and <italic>ENDOU</italic> serve as independent survival markers in HNSCC. In-vitro <italic>ENDOU</italic> overexpression inhibited FaDu and Cal-27 cells proliferation and migration, indicating its tumor-suppressing role in HNSCC progression. GSEA analysis indicated <italic>ENDOU</italic> down-stream pathways like DNA replication, mismatch repair, cell cycle and IL-17 signaling pathway. <italic>ENDOU</italic> showed relative lower expression in HNSCC, especially HPV-positive HNSCC samples. At last, <italic>ENDOU showed</italic> negative correlation with tumor purity and tumor infiltrating macrophages, especially M2 macrophages.</p></sec><sec><title>Conclusion</title><p>This study identified <italic>ENDOU</italic> as a biomarker with prognostic significance in HNSCC progression.</p></sec>