Relationship between expression of EGFR in gastric cancer tissue and clinicopathological features

Gao, Ming; Liang, Xue; Zhang, Zisen; Ma, Wei; Chang, Zhiwei; Zhang, Mingzhi

doi:10.1016/s1995-7645(13)60054-1

Cited by 17 publications

(14 citation statements)

References 15 publications

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“…Amplification of CDK13 was found to associate with gastric and liver cancers [23] . High EGFR and PAK1 expression levels are closely correlated to the incidence and development of gastric cancer in East Asians [24] , [25] while an unanticipated role for STK17A as a candidate promoter of cell proliferation and survival was recently identified [26] . On the other hand, 44% of these cell lines have gene copy number loss in MAP3K15 , an apoptosis-facilitating factor [27] , and RPS6KA6 , a potent tumor suppressor in multiple cancers [28] .…”

Section: Resultsmentioning

confidence: 99%

Molecular Integrative Clustering of Asian Gastric Cell Lines Revealed Two Distinct Chemosensitivity Clusters

Choong

Tan

et al. 2014

PLoS ONE

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Cell lines recapitulate cancer heterogeneity without the presence of interfering tissue found in primary tumor. Their heterogeneous characteristics are reflected in their multiple genetic abnormalities and variable responsiveness to drug treatments. In order to understand the heterogeneity observed in Asian gastric cancers, we have performed array comparative genomic hybridization (aCGH) on 18 Asian gastric cell lines. Hierarchical clustering and single-sample Gene Set Enrichment Analysis were performed on the aCGH data together with public gene expression data of the same cell lines obtained from the Cancer Cell Line Encyclopedia. We found a large amount of genetic aberrations, with some cell lines having 13 fold more aberrations than others. Frequently mutated genes and cellular pathways are identified in these Asian gastric cell lines. The combined analyses of aCGH and expression data demonstrate correlation of gene copy number variations and expression profiles in human gastric cancer cells. The gastric cell lines can be grouped into 2 integrative clusters (ICs). Gastric cells in IC1 are enriched with gene associated with mitochondrial activities and oxidative phosphorylation while cells in IC2 are enriched with genes associated with cell signaling and transcription regulations. The two clusters of cell lines were shown to have distinct responsiveness towards several chemotherapeutics agents such as PI3 K and proteosome inhibitors. Our molecular integrative clustering provides insight into critical genes and pathways that may be responsible for the differences in survival in response to chemotherapy.

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Section: Resultsmentioning

confidence: 99%

Molecular Integrative Clustering of Asian Gastric Cell Lines Revealed Two Distinct Chemosensitivity Clusters

Choong

Tan

et al. 2014

PLoS ONE

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“…In other examples, the SRC gene is a well-known oncogene involved in the PI-3K cascade but no other method is able to detect any significance while oncodomain hotspots identify 8 somatic variants in oncodomain hotspots for LIHC, LUAD, SKCM, and UCEC where some evidence of SRC ’s role is known [129–131]. Even for genes that were significant in MutSigCV, oncodomain hotspots are more sensitive as they identify those same genes as significant in more cancer types for which they are known to play a role like BRAF in STAD [132–134], GBM [135–137], and UCEC [138,139] and EGFR in COAD [111,112], STAD [140,141], and SKCM [142–144]. Indicating the ability of oncodomain hotspots to implicate rare variants, 48 variants on these PKc genes that were found in three or fewer tumor samples fell into oncodomain hotspots and five of these variants were found in only a single tumor sample.…”

Section: Discussionmentioning

confidence: 99%

Oncodomains: A protein domain-centric framework for analyzing rare variants in tumor samples

et al. 2017

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The fight against cancer is hindered by its highly heterogeneous nature. Genome-wide sequencing studies have shown that individual malignancies contain many mutations that range from those commonly found in tumor genomes to rare somatic variants present only in a small fraction of lesions. Such rare somatic variants dominate the landscape of genomic mutations in cancer, yet efforts to correlate somatic mutations found in one or few individuals with functional roles have been largely unsuccessful. Traditional methods for identifying somatic variants that drive cancer are ‘gene-centric’ in that they consider only somatic variants within a particular gene and make no comparison to other similar genes in the same family that may play a similar role in cancer. In this work, we present oncodomain hotspots, a new ‘domain-centric’ method for identifying clusters of somatic mutations across entire gene families using protein domain models. Our analysis confirms that our approach creates a framework for leveraging structural and functional information encapsulated by protein domains into the analysis of somatic variants in cancer, enabling the assessment of even rare somatic variants by comparison to similar genes. Our results reveal a vast landscape of somatic variants that act at the level of domain families altering pathways known to be involved with cancer such as protein phosphorylation, signaling, gene regulation, and cell metabolism. Due to oncodomain hotspots’ unique ability to assess rare variants, we expect our method to become an important tool for the analysis of sequenced tumor genomes, complementing existing methods.

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“…Highly expressed EGFR is related to poor prognosis [9]. Most of the tumors with a highly expressed EGFR often exhibit evident malignant biological behavior, and the highly expressed EGFR is an independent risk factor and marker of poor prognosis [10]. By detecting the EGFR expression in gastric CTs, Mizukami et al [11] found that the positive rate is 46%, and the positive expression is related to tumor size, differentiation grade, and lymphatic metastasis.…”

Section: Discussionmentioning

confidence: 99%

The association between EGFR expression and clinical pathology characteristics in gastric cancer

Chen

Guo

2016

Open Life Sciences

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ObjectiveThe aim of this study was to investigate epidermal growth factor receptor (EGFR) expression in the gastric cancer tissues and the association of EGFR expression with clinical pathology characteristics.MethodsWe firstly analyzed the copy number alteration of EGFR gene in gastric cancer by utilizing the online TCGA resources. We then gathered 71 cases of gastric cancer patients from February 2010 to February 2015 in our hospital. The cancer tissues and normal gastric tissues were tested for EGFR expression by immunohistochemical (IHC) staining and western blotting methods. The association of EGFR expression with clinical pathology characteristics and the prognosis value of EGFR expression were evaluated by the statistical software.ResultsThe copy number of EGFR gene was found to be increased in gastric cancer patients. Western blotting confirmed that EGFR protein was obviously upregulated in tested gastric cancer tissues. Additionally, our IHC results showed that the positive rates of EGFR expression in gastric carcinoid tumors (CTs) and distant normal gastric tissues were 45.1% (32/71) and 25.0% (9/36), respectively. The former was significantly higher than the latter (P < 0.05). The EGFR-positive expression in CTs was related to tumor size, invasion depth, and lymphatic metastasis. The median survival of the EGFR-positive patients was 15.6 months, which was less than that (23.0 months) of the EGFR-negative patients [HR = 2.12, 95%CI: 1.29-4.10 (P < 0.05)]. Also, online survival analysis showed that high expression of EGFR predicted shorter overall survival of gastric cancer patients.ConclusionEGFR was highly expressed in gastric cancer tissues and associated with poor prognosis.

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Relationship between expression of EGFR in gastric cancer tissue and clinicopathological features

Abstract: EGFR expression level in gastric cancer is closely related to the incidence and development of gastric cancer, which can provide a theoretical basis for the targeted therapy for gastric cancer with EGFR as the target.

Cited by 17 publications

References 15 publications

Molecular Integrative Clustering of Asian Gastric Cell Lines Revealed Two Distinct Chemosensitivity Clusters

Molecular Integrative Clustering of Asian Gastric Cell Lines Revealed Two Distinct Chemosensitivity Clusters

Oncodomains: A protein domain-centric framework for analyzing rare variants in tumor samples

The association between EGFR expression and clinical pathology characteristics in gastric cancer

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