Dataset Information

Identification of SERPINE1, PLAU and ACTA1 as biomarkers of head and neck squamous cell carcinoma based on integrated bioinformatics analysis.

ABSTRACT: BACKGROUND:Head 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. 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 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. RESULTS:A 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. 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.

SUBMITTER: Yang K

PROVIDER: S-EPMC6687676 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Identification of SERPINE1, PLAU and ACTA1 as biomarkers of head and neck squamous cell carcinoma based on integrated bioinformatics analysis.

Yang Ke K Zhang Shizhou S Zhang Dongsheng D Tao Qian Q Zhang Tianqi T Liu Guijun G Liu Xingguang X Zhao Tengda T

International journal of clinical oncology 20190401 9

<h4>Background</h4>Head 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.<h4>Methods</h4>Gene expression profiles (GSE6631, GSE58911) and the Cancer Genome Atlas (TCGA) HNSCC data were used for integrated bioinformatics analysis; the differentially expressed gen ...[more]

PMID: 30937621

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Project description:Human papillomavirus (HPV) is an accepted cause of head and neck squamous cell carcinoma (HNSCC), and patients with HPV-associated HNSCC have a favorable prognosis. Currently, there is no general guidance on the most appropriate biomarkers for clinical assessment of HPV in these malignancies. We compared PCR-based and serologic HPV assays, as well as p16 immunohistochemistry, individually and in combination in a single population-based study to assess their associations with overall survival among patients with HNSCC, and thus their potential value as biomarkers. HPV16 serology was determined for 488 patients; immunohistochemical detection of p16 expression in tumors was conducted in a subset of 233 cases, and PCR-based methods to assess the presence of HPV16 DNA in a subset of 179 cases of tumors. Considering each biomarker individually in the subset of patients studied for all endpoints, seropositivity for the E6 and E7 proteins was significantly associated with enhanced all-cause survival in oropharyngeal disease [HR(E6/E7+) = 0.1, 95% confidence interval (CI) = 0.02-0.3]. Neither the presence of HPV16 DNA nor p16 immunostaining was associated with significant enhanced overall survival in oropharyngeal disease (HR(DNA) = 0.9, 95% CI = 0.3-2.9; HR(p16) = 0.3, 95% CI = 0.1-1.1). However, the combination of HPV-positive DNA and E6 or E7 serology was associated with enhanced overall survival in oropharyngeal disease (HR(DNA+/E6/E7+) = 0.1, 95% CI = 0.02-1.0), whereas E6/E7 seronegative patients with evidence of HPV in tumor DNA did not show any evidence of favorable survival (HR(DNA+/E6-/E7-) = 3.4, 95% CI = 0.6-18.1). Furthermore, patients with p16 staining and E6 or E7 seropositivity had favorable survival from oropharyngeal disease (HR(p16+/E6/E7+) = 0.1, 95% CI = 0.02-0.4), whereas patients who were p16 positive and E6/E7 seronegative had significantly increased hazard of all causes of death (HR(p16+/E6-/E7-) = 3.1, 95% CI = 1.2-7.7). A stronger association of HPV presence with prognosis (assessed by all-cause survival) is observed when "HPV-associated" HNSCC is defined using tumor status (HPV DNA status or P16) and HPV E6/E7 serology in combination rather using tumor HPV status alone.

Dataset Information

Identification of SERPINE1, PLAU and ACTA1 as biomarkers of head and neck squamous cell carcinoma based on integrated bioinformatics analysis.

Publications

Identification of SERPINE1, PLAU and ACTA1 as biomarkers of head and neck squamous cell carcinoma based on integrated bioinformatics analysis.

Similar Datasets

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