Dataset Information

Expression Analysis of GRHL3 and PHLDA3 in Head and Neck Squamous Cell Carcinoma.

ABSTRACT: Background:Head and neck squamous cell carcinoma (HNSCC) includes a group of heterogeneous tumors with generally invasive behavior. The PI3K/AKT pathway plays an important role in the pathogenesis of HNSCC. Methods:In the current study, we investigated the expression of two negative feedback regulators of the PI3K pathway, namely PHLDA3 and GRHL3, in 45 paired samples of HNSCC and adjacent non-cancerous tissues (ANCTs). Results:While expression of GRHL3 was down-regulated in tumoral tissues compared with ANCTs by the factor 4.21, PHLDA3 expression levels were up-regulated by 5.99-times. Gender-based analysis revealed a significant down-regulation of GRHL3 gene expression level in male patients compared with the control samples and significant up-regulation of PHLDA3 gene expression level in both sexes compared with the control samples. Differences in the expressions of both genes were significant in patients aged more than 60 years, but not in the younger patients. Expression of GRHL3 was only down-regulated in patients with positive smoking history. Expression of GRHL3 was decreased in grades 2 and 3 samples compared with controls. There was a significant increase in transcript levels of PHLDA3 in stages II and III HNSCC samples compared with the controls group. ROC curve analysis indicated that the expression level of PHLDA3 could be a promising marker for the diagnosis of HNSCC patients with a sensitivity and specificity of 0.666 and 0.688, respectively. In addition, sensitivity and specificity of GRHL3 were 0.755 and 0.577, respectively. Discussion:The current study indicates dysregulation of regulators of PI3K pathway in HNSCC and their potential application as putative biomarkers for this cancer.

SUBMITTER: Saffarzadeh N

PROVIDER: S-EPMC7276198 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Expression Analysis of <i>GRHL3</i> and <i>PHLDA3</i> in Head and Neck Squamous Cell Carcinoma.

Saffarzadeh Negin N Ghafouri-Fard Soudeh S Rezaei Zahra Z Aghazadeh Keyvan K Yazdani Farzad F Mohebi Mehdi M Ahmadi Mohsen M Shakoori Abbas A Tavakkoly-Bazzaz Javad J

Cancer management and research 20200602

<h4>Background</h4>Head and neck squamous cell carcinoma (HNSCC) includes a group of heterogeneous tumors with generally invasive behavior. The PI3K/AKT pathway plays an important role in the pathogenesis of HNSCC.<h4>Methods</h4>In the current study, we investigated the expression of two negative feedback regulators of the PI3K pathway, namely <i>PHLDA3</i> and <i>GRHL3</i>, in 45 paired samples of HNSCC and adjacent non-cancerous tissues (ANCTs).<h4>Results</h4>While expression of <i>GRHL3</i> ...[more]

PMID: 32581582

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Project description:AbstractMicroRNAs (miRNAs) play critical roles in carcinogenesis and development of cancers. In this study, we analyzed the eccentrically expressed miRNAs in head and neck squamous cell carcinoma (HNSCC) tissues based on the miRNA-Seq data of HNSCC patients available in the Cancer Genome Atlas database. Aberrant expression of 2589 miRNAs was detected in HNSCC tissues (1128 downregulated and 1461 upregulated). The differential expression levels of the miRNAs were further validated by analysis of 25 HNSCC samples and paired control tissues and compared with the Gene Expression Omnibus database to determine the candidate miRNAs. Quantitative reverse transcription polymerase chain reaction was used to compare the expression of these candidate miRNAs between 22 fresh HNSCC tissue samples and 11 control samples. In addition, the relationship between the expression of these candidate miRNAs and Tumor, Node, Metastases staging of HNSCC was analyzed. Compared with the expression in control tissues, the levels of hsa-miR-410-3p, hsa-miR-411-5p, hsa-miR-125b-2-3p, and hsa-miR-99a-3p were significantly lower in HNSCC. According to the Cancer Genome Atlas dataset analyzed, all 4 miRNAs were shown to inhibit tumor progression (T stage), positive lymph node metastasis (N stage), and distant metastasis (M stage) in HNSCC. Kyoto Encyclopedia of Genes and Genomes analysis showed that genes regulated by these 4 miRNAs were enriched in certain pathways, including the transforming growth factor-β signaling pathway and the Hippo pathway. Enriched gene ontology terms mainly included regulation of transcription, cell proliferation, and apoptosis, which are well-characterized functions of miRNAs. Moreover, all 4 miRNAs inhibited the progression of primary tumors (T stage) and metastasis of regional lymph nodes (N stage). The top 4 aberrantly expressed miRNAs identified in this study have great clinical value in developing strategies for early diagnosis and treatment of HNSCC. More intensive studies are required to elucidate the mechanism underlying the roles of these miRNAs in HNSCC.

Dataset Information

Expression Analysis of GRHL3 and PHLDA3 in Head and Neck Squamous Cell Carcinoma.

Publications

Expression Analysis of <i>GRHL3</i> and <i>PHLDA3</i> in Head and Neck Squamous Cell Carcinoma.

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