Abstract

BackgroundThe cause and underlying molecular mechanisms of head and neck squamous cell carcinoma (HNSCC) are unclear. Our study aims to identify the key genes associated with HNSCC and reveal potential biomarkers.MethodsIn this study, the expression profile dataset GSE83519 of the Gene Expression Omnibus database and the RNA sequencing dataset of HNSCC of The Cancer Genome Atlas were included for analysis. Sixteen differentially expressed genes were screened from these two datasets using R software. Gene Expression Profiling Interactive Analysis 2 (GEPIA2) was then adopted for survival analysis, and finally, three key genes related to the overall survival of HNSCC patients were identified. Furthermore, we verified these three genes using the Oncomine database and from real-time PCR and immunohistochemistry results from HNSCC tissues.ResultsThe expression data of 44 samples from GSE83519 and 545 samples from TCGA-HNSC were collected. Using bioinformatics, the two databases were integrated, and 16 DEGs were screened out. Gene Ontology (GO) enrichment analysis showed that the biological functions of DEGs focused primarily on the apical plasma membrane and regulation of anoikis. Kyoto Encyclopedia of Genes and Genomes (KEGG) signalling pathway analysis showed that these DEGs were mainly involved in drug metabolism-cytochrome P450 and serotonergic synapses. Survival analysis identified three key genes, CEACAM5, CEACAM6 and CLCA4, that were closely related to HNSCC prognosis. The Oncomine database, qRT–PCR and IHC verified that all 3 key genes were downregulated in most HNSCC tissues compared to adjacent normal tissues.ConclusionsThis study indicates that integrated bioinformatics analyses play an important role in screening for differentially expressed genes and pathways in HNSCC, helping us better understand the biomarkers and molecular mechanism of HNSCC.

Highlights

  • The cause and underlying molecular mechanisms of head and neck squamous cell carcinoma (HNSCC) are unclear

  • Real‐time PCR TRIzol reagent (Invitrogen, USA) was used to extract total RNA from the tissues. cDNA obtained from the reverse transcription of the RNA was used as templates for detecting the expression levels of the three key genes we identified, carcinoembryonic antigen-related cell adhesion molecule-5 (CEACAM5), carcinoembryonic antigen-related cell adhesion molecule-6 (CEACAM6) and chloride channel accessory 4 (CLCA4)

  • According to the analysis by several R software packages, 827 differentially expressed genes (DEGs) were obtained from the GSE83519 dataset

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Summary

Introduction

The cause and underlying molecular mechanisms of head and neck squamous cell carcinoma (HNSCC) are unclear. With over 800,000 new cases each year, are among the most common malignancies in the world [1]. Squamous cell carcinoma accounts for more than 90% of these cancers. Continuous exposure to tobacco, tobacco-like products and alcohol is thought to increase the risk of head and neck squamous cell. Ye et al Cancer Cell Int (2021) 21:549 carcinoma (HNSCC) [2]. The crucial treatment strategy includes surgery, radiotherapy and chemotherapy. The incidence of tumour recurrence after standard treatment is 15–50% [4]. In addition to HPV status, biomarkers for precise targets of HNSCC treatment have yet to be elucidated [5]

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