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

Chengzhi Xu; Yunbin Zhang; Yupeng Shen; Yong Shi; Ming Zhang; Liang Zhou

doi:10.3389/fonc.2020.522332

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

Front Oncol. 2021 Feb 5:10:522332. doi: 10.3389/fonc.2020.522332. eCollection 2020.

Authors

Chengzhi Xu¹, Yunbin Zhang^{2

3}, Yupeng Shen⁴, Yong Shi¹, Ming Zhang¹, Liang Zhou¹

Affiliations

¹ Department of Otolaryngology-Head and Neck Surgery, Eye Ear Nose and Throat Hospital, Fudan University, Shanghai, China.
² Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
³ Department of Respirology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
⁴ Department of Otolaryngology-Head and Neck Surgery, Bethune International Peace Hospital, Shijiazhuang, China.

Abstract

Background: 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.

Methods: 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. ENDOU 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.

Results: 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 COBL and ENDOU serve as independent survival markers in HNSCC. In-vitro ENDOU overexpression inhibited FaDu and Cal-27 cells proliferation and migration, indicating its tumor-suppressing role in HNSCC progression. GSEA analysis indicated ENDOU down-stream pathways like DNA replication, mismatch repair, cell cycle and IL-17 signaling pathway. ENDOU showed relative lower expression in HNSCC, especially HPV-positive HNSCC samples. At last, ENDOU showed negative correlation with tumor purity and tumor infiltrating macrophages, especially M2 macrophages.

Conclusion: This study identified ENDOU as a biomarker with prognostic significance in HNSCC progression.

Keywords: ENDOU; bioinformatics; head and neck squamous cell carcinoma; prognosis; tumor suppressor.