Abstract
BackgroundDNA methylation and miRNA-target genes play an important part in the early development of various tumors and have been studied as tumor biomarkers. Although previous studies have reported a cluster of molecular events (such as aberrant alterations of genomics and epigenetics), little is known of the potential biomarkers for early diagnosis and prognostic evaluation in head and neck squamous cell carcinoma (HNSCC).MethodsMultiple bioinformatics tools based on The Cancer Genome Atlas (TCGA) database and clinical samples were applied to evaluate the beneficial biomarkers in HNSCC. We focused on the role of plasminogen activator urokinase (PLAU), including diagnostic and prognostic significance, gene expression analysis, aberrant DNA methylation characteristics, interaction of miRNAs and associated signaling pathways.ResultsWe found that PLAU was aberrantly upregulated in HNSCC, regardless of the mRNA or protein level. The results of receiver operating characteristic (ROC) curve and Cox regression analysis revealed that PLAU was a diagnostic and independent prognostic factor for patients with HNSCC. Hypomethylation of PLAU was closely related to poor survival in HNSCC. Additionally, miR-23b-3p was predicted to target PLAU and was significantly downregulated in HNSCC tissues. Therefore, our findings suggested that PLAU functioned as a promoter in the pathological process of HNSCC. DNA hypomethylation and downregulation of miR-23b-3p were associated with PLAU overexpression. Finally, our findings provided evidence of a significant interaction between PLAU-target and miRNAs-target pathways, indicating that miR-23b-3p suppresses malignant properties of HNSCC by targeting PLAU via Ras/MAPK and Akt/mTOR signaling pathways.ConclusionsPLAU is overexpressed and may serve as an independent diagnostic and prognostic biomarker in HNSCC. Hypomethylation and downregulation of miR-23b-3p might account for the oncogenic role of PLAU in HNSCC.
Highlights
DNA methylation and miRNA-target genes play an important part in the early development of various tumors and have been studied as tumor biomarkers
Gene expression profile analysis and plasminogen activator urokinase (PLAU) filtering The adjusted p value was analyzed to correct for false positive results in The Cancer Genome Atlas (TCGA) or Gene Expression Omnibus (GEO)
Hypomethylation of PLAU in Head and neck squamous cell carcinomas (HNSCCs) To further clarify the mechanism underlying the overexpression of PLAU in HNSCC we investigated the methylation status via multiple tools
Summary
DNA methylation and miRNA-target genes play an important part in the early development of various tumors and have been studied as tumor biomarkers. Previous studies have reported a cluster of molecular events (such as aberrant alterations of genomics and epigenetics), little is known of the potential biomarkers for early diagnosis and prognostic evaluation in head and neck squamous cell carcinoma (HNSCC). Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide [1]. For patients with HNSCC, prognosis prediction is crucial to be considered suitable for personalized treatment by physicians. Clinical parameters such as the primary tumor, regional lymph nodes, and metastasis (TNM) classification are applied to predict the outcome and make therapeutic decisions, they have a low accuracy of prediction in many situations [5, 6]. It is urgent to identify novel prognostic biomarkers to improve survival for patients with HNSCC
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