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Distinct expression and prognostic value of members of the epidermal growth factor receptor family in ovarian cancer.

ABSTRACT: Background:Increased aberrant expression or activation of the epidermal growth factor receptor (EGFR) family members has been reported in a wide range of cancers, and the EGFR family of tyrosine kinases has emerged as an important therapeutic target in malignancies. However, the expression patterns and exact roles of each distinct EGFR family member, which contribute to tumorigenesis and progression of ovarian cancer (OC), are yet to be elucidated. Materials and methods:In the current study, we report the distinct expression and prognostic value of EGFR family members in patients with OC by analyzing a series of databases including ONCOMINE, Gene Expression Profiling Interactive Analysis, Kaplan-Meier plotter, cBioPortal, and Database for Annotation, Visualization and Integrated Discovery . Results:It was found that in patients with OC, mRNA expression levels of ERBB2/3/4 were significantly upregulated, whereas the transcription levels of EGFR were downregulated. Aberrant EGFR expression and ERBB2/3/4 mRNA levels were associated with OC prognosis. Conclusion:These results suggest that EGFR and ERBB3/4 are distinct prognostic biomarkers and may be potential targets for OC. These results may be beneficial to better understand the molecular underpinning of OC and may be useful to develop tools for more accurate OC prognosis and for promoting the development of EGFR-targeted inhibitors for OC treatment.

SUBMITTER: Zhou Q

PROVIDER: S-EPMC6300368 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Distinct expression and prognostic value of members of the epidermal growth factor receptor family in ovarian cancer.

Zhou Quan Q Hou Chao-Nan CN Yang Huai-Jie HJ He Ze Z Zuo Man-Zhen MZ

Cancer management and research 20181213

<h4>Background</h4>Increased aberrant expression or activation of the epidermal growth factor receptor (<i>EGFR</i>) family members has been reported in a wide range of cancers, and the <i>EGFR</i> family of tyrosine kinases has emerged as an important therapeutic target in malignancies. However, the expression patterns and exact roles of each distinct <i>EGFR</i> family member, which contribute to tumorigenesis and progression of ovarian cancer (OC), are yet to be elucidated.<h4>Materials and m ...[more]

PMID: 30588099

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Project description:The majority of borderline ovarian tumours (BOTs) behave in a benign fashion, but some may show aggressive behavior. The reason behind this has not been elucidated. The epidermal growth factor receptor (EGFR) is known to contribute to cell survival signals as well as metastatic potential of some tumours. EGFR expression and gene status have not been thoroughly investigated in BOTs as it has in ovarian carcinomas. In this study we explore protein expression as well as gene mutations and amplifications of EGFR in BOTs in comparison to a subset of other epithelial ovarian tumours. We studied 85 tumours, including 61 BOTs, 10 low grade serous carcinomas (LGSCs), 9 high grade serous carcinomas (HGSCs) and 5 benign epithelial tumours. EGFR protein expression was studied using immunohistochemistry. Mutations were investigated by Sanger sequencing exons 18-21 of the tyrosine kinase domain of EGFR. Cases with comparatively higher protein expression were examined for gene amplification by chromogenic in situ hybridization. We also studied the tumours for KRAS and BRAF mutations. Immunohistochemistry results revealed both cytoplasmic and nuclear EGFR expression with variable degrees between tumours. The level of nuclear localization was relatively higher in BOTs and LGSCs as compared to HGSCs or benign tumours. The degree of nuclear expression of BOTs showed no significant difference from that in LGSCs (mean ranks 36.48, 33.05, respectively, p=0.625), but was significantly higher than in HGSCs (mean ranks: 38.88, 12.61 respectively, p< 0.001) and benign tumours (mean ranks: 35.18, 13.00 respectively, p= 0.010). Cytoplasmic expression level was higher in LGSCs. No EGFR gene mutations or amplification were identified, yet different polymorphisms were detected. Five different types of point mutations in the KRAS gene and the V600E BRAF mutation were detected exclusively in BOTs and LGSCs. Our study reports for the first time nuclear localization of EGFR in BOTs. The nuclear localization similarities between BOTs and LGSCs and not HGSCs support the hypothesis suggesting evolution of LGSCs from BOTs. We also confirm that EGFR mutations and amplifications are not molecular events in the pathogenesis of BOTs.

Dataset Information

Distinct expression and prognostic value of members of the epidermal growth factor receptor family in ovarian cancer.

Publications

Distinct expression and prognostic value of members of the epidermal growth factor receptor family in ovarian cancer.

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