Prognostic role of DFNA5 in head and neck squamous cell carcinoma revealed by systematic expression analysis

Abstract Background The gasdermin E gene (GSDME, also known as DFNA5) is mutated in familial aging-related hearing loss. Recent studies have also revealed that the expression of DFNA5 is suppressed in many cancer types; however, little is known about the function of DFNA5 in head and neck squamous cell carcinoma (HNSCC). Accordingly, the aim of the present study was to evaluate the expression of DFNA5 and explore its prognostic value in HNSCC. Result We used a set of bioinformatics tools, including Oncomine, TIMER, TISIDB, cBioPortal, and GEPIA, to analyze the expression of DFNA5 in patients with HNSCC from public databases. Kaplan-Meier plotter was used to evaluate the potential prognostic significance of DFNA5. DFNA5 mRNA levels were significantly higher in HNSCC tissues than in normal tissues, and high DFNA5 expression was correlated with worse survival. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that DFNA5 expression has a strong positive correlation with cell adhesion and the integrin signaling pathway, whereas its expression was negatively correlated with the levels of infiltrating B cells (cor = − 0.223, P = 8.57e-07) and CD8 T cells (cor = − 0.223, P = 2.99e-07). Conclusion This study demonstrates that DFNA5 expression has prognostic value for HNSCC patients. Moreover, these results suggest that regulation of lymphocyte infiltration is the mechanism underlying the function of DFNA5 in HNSCC.

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Prognostic Role of DFNA5 in Head and Neck Squamous Cell Carcinoma Revealed by Systematic Expression Analysis

10.21203/rs.3.rs-114898/v1 ◽

2020 ◽

Author(s):

Zhiguo Liu ◽

Hongyan Liu ◽

Qian Dong ◽

Hongyu Li ◽

Bin Zhang ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Prognostic Value ◽

Prognostic Significance ◽

Neck Squamous Cell Carcinoma ◽

Mrna Levels ◽

Strong Positive Correlation ◽

Normal Tissues

Abstract The gasdermin E gene (GSDME, also known as DFNA5) is mutated in familial aging-related hearing loss. Recent studies have also revealed that the expression of DFNA5 is suppressed in many cancer types; however, little is known about the function of DFNA5 in head and neck squamous cell carcinoma (HNSCC). Accordingly, the aim of the present study was to evaluate the expression of DFNA5 and explore its prognostic value in HNSCC. We used a set of bioinformatics tools, including Oncomine, TIMER, TISIDB, cBioPortal, and GEPIA, to analyze the expression of DFNA5 in patients with HNSCC from public databases. Kaplan-Meier plotter was used to evaluate the potential prognostic significance of DFNA5. DFNA5 mRNA levels were significantly higher in HNSCC tissues than in normal tissues, and high DFNA5 expression was correlated with worse survival. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that DFNA5 expression has a strong positive correlation with cell adhesion and the integrin signaling pathway, whereas its expression was negatively correlated with the levels of infiltrating B cells (cor = –0.223, P = 8.57e-07) and CD8 T cells (cor = –0.223, P = 2.99e-07). Overall, this study demonstrates that DFNA5 expression has prognostic value for HNSCC patients. Moreover, these results suggest that regulation of lymphocyte infiltration is the mechanism underlying the function of DFNA5 in HNSCC.

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Transcriptional Expressions of Matrix Metalloproteinase and Their Diagnostic and Prognostic Significance in Head and Neck Squamous Cell Carcinoma

SSRN Electronic Journal ◽

10.2139/ssrn.3736014 ◽

2020 ◽

Author(s):

Pan Ting ◽

Jingrong Cheng ◽

Ying Yin ◽

Jiaqi Wang ◽

Xiaoru Mao ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Matrix Metalloproteinase ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Prognostic Significance ◽

Neck Squamous Cell Carcinoma

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Differential expression and prognostic value of long non-coding RNA in HPV-negative head and neck squamous cell carcinoma

Head & Neck ◽

10.1002/hed.25136 ◽

2018 ◽

Vol 40 (7) ◽

pp. 1555-1564 ◽

Cited By ~ 17

Author(s):

Sulsal-Ul Haque ◽

Liang Niu ◽

Damaris Kuhnell ◽

Jacob Hendershot ◽

Jacek Biesiada ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Differential Expression ◽

Squamous Cell ◽

Prognostic Value ◽

Neck Squamous Cell Carcinoma ◽

Non Coding Rna ◽

Long Non Coding Rna

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PROGNOSTIC VALUE OF MX1 IN HEAD AND NECK SQUAMOUS CELL CARCINOMA

Oral Surgery Oral Medicine Oral Pathology and Oral Radiology ◽

10.1016/j.oooo.2017.06.074 ◽

2017 ◽

Vol 124 (3) ◽

pp. e220

Author(s):

C. DONNELLY ◽

L. DONNELLY ◽

Y. XIE ◽

OKEMOS E. BELLILE ◽

G. WOLF ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Prognostic Value ◽

Neck Squamous Cell Carcinoma

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Prognostic Significance of Extranodal Extension in Head and Neck Squamous Cell Carcinoma cN0 Patients With Occult Metastatic Neck Nodes

Acta Otorrinolaringologica (English Edition) ◽

10.1016/j.otoeng.2017.07.002 ◽

2018 ◽

Vol 69 (3) ◽

pp. 156-164 ◽

Cited By ~ 1

Author(s):

Joan Lop ◽

Antoni Rigó ◽

Alberto Codina ◽

Julia de Juan ◽

Miquel Quer ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Prognostic Significance ◽

Neck Squamous Cell Carcinoma ◽

Extranodal Extension

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

Frontiers in Oncology ◽

10.3389/fonc.2020.522332 ◽

2021 ◽

Vol 10 ◽

Author(s):

Chengzhi Xu ◽

Yunbin Zhang ◽

Yupeng Shen ◽

Yong Shi ◽

Ming Zhang ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Prognostic Significance ◽

Neck Squamous Cell Carcinoma ◽

Integrated Analysis ◽

Pathway Enrichment Analysis ◽

And Migration ◽

Proliferation And Migration

BackgroundHead 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.MethodsWe 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.ResultsNinety-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.ConclusionThis study identified ENDOU as a biomarker with prognostic significance in HNSCC progression.

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