Tyrosine kinase domain mutations of &lt;em&gt;EGFR&lt;/em&gt; gene in head and neck squamous cell carcinoma

Vatte, Chittibabu; Amri, Ali M Al; Cyrus, Cyril; Chathoth, Shahanas; Acharya, Sadananda; Hashim, Tariq Mohammad; Ali, Zhara Al; Alshreadah, Saleh Tawfeeq; Alsayyah, Ahmed; Al-Ali, Amein K.

doi:10.2147/ott.s132187

Cited by 18 publications

(16 citation statements)

References 38 publications

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“…Reviewing the recent literature, we find that the overexpression of The epidermal growth factor receptor (EGFR) has been noted in up to 90% of HNSCC [43]and the EGFR mutation was associated with the grading and staging of HNSCC[44]. EGFR inhibitors -monoclonal antibodies (mAbs) include cetuximab, panitumumab, zalutumumab and nimotuzumab.…”

Section: Discussionmentioning

confidence: 99%

Identification of Potential Biomarkers and Survival Analysis for Head and Neck Squamous Cell Carcinoma Using Bioinformatics Strategy: A Study Based on TCGA and GEO Datasets

Shen

Liu

Zhang

et al. 2019

BioMed Research International

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The mechanism and gene markers of head and neck squamous cell carcinoma (HNSCC), a common malignant tumor, have not yet been identified. The aim of this study was to identify the key genes and pathways associated with HNSCC and to further analyze its molecular mechanism and prognostic significance. In this study, the expression profile chip data GSE6631 from Gene Expression Omnibus (GEO) included paired HNSCC tumor and normal samples from 22 patients; the RNAseq tertiary dataset of HNSCC and corresponding clinical information from The Cancer Genome Atlas (TCGA) included biological information of 12 normal head and neck tissues and 111 HNSCC sample tissues. Differentially expressed genes (DEGs) were screened by R software, and the pathway enrichment analysis of DEGs was performed by DAVID, String, and Sytoscape software programs. Combining the GEO and the TCGA databases, we used bioinformatics technology to screen out 50 DEGs in HNSCC and enrich the biological functions and key pathways of HNSCC. Then we performed Gene Ontology (GO) enrichment analysis, the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis, protein-protein interaction (PPI) analysis, and survival analysis on these DEGs. Using CMap, we identified candidate small molecules that might reverse HNSCC gene expression. Finally, four most important small molecules that could provide more reliable biomarkers for early diagnosis and individualized control of HNSCC were identified.

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Section: Discussionmentioning

confidence: 99%

Identification of Potential Biomarkers and Survival Analysis for Head and Neck Squamous Cell Carcinoma Using Bioinformatics Strategy: A Study Based on TCGA and GEO Datasets

Shen

Liu

Zhang

et al. 2019

BioMed Research International

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“…RTK signaling induces the activation of Ras/mitogen-activated protein kinase and the Ras/PI3K/protein kinase B (AKT) signaling pathways, resulting in increased proliferation, survival and metastasis of cancer cells. Somatic mutations in RTKs, Ras, B-Raf, PI3K and AKT are commonly observed in various cancer types (25,26). Thus, research has focused on the genetic alterations in the genes involved in these pathways for use in targeted therapy.…”

Section: Discussionmentioning

confidence: 99%

Helical and kinase domain mutations of PIK3CA, and their association with hormone receptor expression in breast cancer

et al. 2019

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Breast cancer is one of the major causes of female morbidity and mortality, accounting for ~25% of the total cancer cases in women. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic α subunit ( PIK3CA ) mutations serve a major role in downstream signaling of receptor tyrosine kinases. The present study aimed to elucidate the frequency of exon 9 and 20 mutations of PIK3CA and their role in disease progression. A total of 118 tumor samples from confirmed breast cancer patients were collected from the histopathology laboratory at King Fahd Hospital of the University (Al-Khobar, Saudi Arabia). Sanger sequencing was performed on extracted DNA to identify the mutations on exons 9 and 20 of PIK3CA . The results were further validated by competitive allele-specific TaqMan polymerase chain reaction. Three mutations, namely E542K and E545K within exon 9, and H1047R within exon 20, were observed in 25 patients (21.2%). Among these, 18 patients carried the H1047R mutation of the kinase domain, while the remaining 7 patients carried mutations in the helical domain. PIK3CA mutations were associated with the estrogen receptor-positive/progesterone receptor-positive (ER + /PR + ) group of tumors in contrast to the ER − /PR − group (P=0.021). Furthermore, it was observed that the PIK3CA mutation was associated with a poor disease prognosis. Taken together, the current study emphasized the potential of PIK3CA mutations as an important biomarker for breast cancer classification and the possible use of PIK3CA inhibitor as targeted therapy for breast cancer.

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“…EGFR activation leads to cell proliferation, metastasis, invasion and angiogenesis via tyrosine kinase mediated activation of PI3K, PTEN/AKT, MAPK, ERK and JAK/STAT pathways. Hence, the activation of EGFR is crucial to the carcinogenesis ( 25 , 26 ). EGFR over expression was observed in >80% of HNSCC subjects ( 13 ); 68.6% ( 27 ) in laryngeal carcinoma and 91.5% in glottic laryngeal carcinoma patients ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

Association of epidermal growth factor receptor protein expression with histopathological and clinical parameters in carcinoma of the larynx

Vatte

Alamri

Cyrus

et al. 2019

Transl. Cancer Res.

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Background Laryngeal cancer is one of the most commonly occurring cancers in head and neck malignancies with the majority of tumors being squamous cell carcinomas. Despite sharing similarities with other head and neck tumors, laryngeal tumors require a special approach in treatment due to the need for organ preservation. Non-surgical procedures, including chemotherapy, radiotherapy and novel targeted therapies are alternative options. However, the selection of appropriate treatment modality is crucial for recurrence-free survival. With the availability of targeted therapies, the biomarker expression pattern has become a vital tool in the selection of treatment and prognosis. The present study aims to study the variation of protein [epidermal growth factor receptor (EGFR), phosphatase and tensin homolog (PTEN) and p16 INK4 ] expression and human papillomavirus (HPV) infection status in larynx carcinoma patients and correlate it with histopathological and clinical parameters. Methods This is a retrospective study comprising laryngeal carcinoma tumor samples from 18 patients. The samples were analyzed for EGFR, PTEN and p16 INK4 expression by immunohistochemistry and HPV status by chromogenic in-situ hybridization (CISH). Results The EGFR over expression was observed in the 83.3% of patients. This high EGFR expression was associated with lymph node positivity (P=0.045) and advanced disease stage (P=0.035). Furthermore, the smoking status of the patients is correlated with a better prognosis (P=0.048). The PTEN was negatively expressed in 94.4% patients. Conclusions The association of EGFR over expression with lymph node status and advanced stage of the disease supports the role that EGFR plays in the tumor metastasis and invasion in laryngeal carcinoma patients. Therefore, the use of anti-EGFR targeted therapy in cases of laryngeal carcinoma may improve the prognosis of these patients. The other studied proteins p16 INK4 , PTEN and HPV infection did not show any correlation with prognosis and other clinical parameters.

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Tyrosine kinase domain mutations of <em>EGFR</em> gene in head and neck squamous cell carcinoma

Cited by 18 publications

References 38 publications

Identification of Potential Biomarkers and Survival Analysis for Head and Neck Squamous Cell Carcinoma Using Bioinformatics Strategy: A Study Based on TCGA and GEO Datasets

Identification of Potential Biomarkers and Survival Analysis for Head and Neck Squamous Cell Carcinoma Using Bioinformatics Strategy: A Study Based on TCGA and GEO Datasets

Helical and kinase domain mutations of PIK3CA, and their association with hormone receptor expression in breast cancer

Association of epidermal growth factor receptor protein expression with histopathological and clinical parameters in carcinoma of the larynx

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