Abstract
BackgroundHead and neck squamous cell carcinoma (HNSCC) is the six leading cancer by incidence worldwide. The 5-year survival rate of HNSCC patients remains less than 65% due to lack of symptoms in the early stage. Hence, biomarkers which can improve detection of HNSCC should improve clinical outcome.MethodsGene expression profiles (GSE6631, GSE58911) and the Cancer Genome Atlas (TCGA) HNSCC data were used for integrated bioinformatics analysis; the differentially expressed genes (DEGs) were then subjected to functional and pathway enrichment analysis, protein–protein interaction (PPI) network construction. Subsequently, module analysis of the PPI network was performed and overall survival (OS) analysis of hub genes in subnetwork was studied. Finally, immunohistochemistry was used to verify the selected markers.ResultsA total of 52 up-regulated and 80 down-regulated DEGs were identified, which were mainly associated with ECM–receptor interaction and focal adhesion signaling pathways. Importantly, a set of prognostic signatures including SERPINE1, PLAU and ACTA1 were screened from DEGs, which could predict OS in HNSCC patients from TCGA cohort. Experiment of clinical samples further successfully validated that these three signature genes were aberrantly expressed in the oral epithelial dysplasia and HNSCC, and correlated with aggressiveness of HNSCC patients.ConclusionsSERPINE1, PLAU and ACTA1 played important roles in regulating the initiation and progression of HNSCC, and could be identified as key biomarkers for precise diagnosis and prognosis of HNSCC, which will provide potential targets for clinical therapies.
Highlights
Head and neck squamous cell carcinoma (HNSCC), which arises from the oral cavity, larynx and pharynx, ranks as the sixth most common malignancy with an estimated 835,000 new cases and 43,000 associated deaths worldwide in 2018 [1, 2]
In the biological process (BP) group, gene ontology (GO) analysis results showed that up-regulated differentially expressed genes (DEGs) were significantly enriched in extracellular matrix organization, collagen catabolic process, extracellular matrix disassembly, cell adhesion and collagen fibril organization; the downregulated DEGs were mainly enriched in muscle contraction and muscle filament sliding
For molecular function (MF), the enrichment of up-regulated DEGs was in metalloendopeptidase activity, extracellular matrix structural constituent, serine-type endopeptidase activity, collagen binding and endopeptidase activity, and down-regulated genes were enriched in structural constituent of muscle
Summary
Head and neck squamous cell carcinoma (HNSCC), which arises from the oral cavity, larynx and pharynx, ranks as the sixth most common malignancy with an estimated 835,000 new cases and 43,000 associated deaths worldwide in 2018 [1, 2]. Microarrays based on high-throughput platforms for analysis of gene expression are increasingly valued as a promising and efficient tool to screen significant genetic alternations in carcinogenesis and identify biomarkers for diagnosis and prognosis of cancer [5]. Methods Gene expression profiles (GSE6631, GSE58911) and the Cancer Genome Atlas (TCGA) HNSCC data were used for integrated bioinformatics analysis; the differentially expressed genes (DEGs) were subjected to functional and pathway enrichment analysis, protein–protein interaction (PPI) network construction. A set of prognostic signatures including SERPINE1, PLAU and ACTA1 were screened from DEGs, which could predict OS in HNSCC patients from TCGA cohort. Conclusions SERPINE1, PLAU and ACTA1 played important roles in regulating the initiation and progression of HNSCC, and could be identified as key biomarkers for precise diagnosis and prognosis of HNSCC, which will provide potential targets for clinical therapies
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