Interpreting the distinct and shared genetic characteristics between Epstein–Barr virus associated and non-associated gastric carcinoma

Wang, Xixun; Zhang, Yifei; Jiang, Lixin; Zhou, Fan; Zhai, Hao‐Ran; Zhang, Menglai; Wang, Jinglin

doi:10.1016/j.gene.2015.11.010

Cited by 4 publications

(5 citation statements)

References 61 publications

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“…Zhao et al showed 13 pathways to be deregulated in EBVaGC, including: neuroactive ligand-receptor interaction, pathways in cancer, mitogen-activated protein kinase (MAPK) signaling pathway, cytokine-cytokine receptor interaction, axon guidance, regulation of actin cytoskeleton, insulin signaling pathway, cell adhesion molecules, endocytosis, calcium signaling pathway, Wnt signaling pathway, glutamatergic synapse, and focal adhesion [26]. These mechanisms are altered to facilitate rapid tumor growth [36]. A gene set enrichment analysis of EBV-specific gene expression signatures using ingenuity pathway analysis by Sohn et al [38] revealed that EBVaGC had significant genetic alterations in pathways involving energy production and metabolism, with a downregulation of metabolism genes.…”

Section: Pathophysiology and Tumorigenesismentioning

confidence: 99%

“…EBV can also activate several important cellular pathways which promote gastric cancer development. Wang et al [36] characterized EBVaGC-specific cellular pathways, and found alterations in macromolecular biosynthetic processes such as carbohydrate, lipid and protein biosynthesis. Deregulation of cholesterol transport and lipoprotein clearance pathways is also evident in EBVaGC [37].…”

Section: Pathophysiology and Tumorigenesismentioning

confidence: 99%

See 1 more Smart Citation

Outlooks on Epstein-Barr virus associated gastric cancer

Naseem

Barzi

Brezden-Masley

et al. 2018

Cancer Treatment Reviews

171

143

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Epstein-Barr virus associated gastric cancer (EBVaGC) comprises approximately 10% of gastric carcinomas. Multiple factors contribute to tumorigenesis, including EBV driven hypermethylation of tumor suppressor genes, inflammatory changes in gastric mucosa, host immune evasion by EBV and changes in cell cycle pathways. The unique molecular characteristics of EBVaGC, such as programmed death ligand 1 (PD-L1) overexpression, highlight the potential for using EBV as a biomarker for response to immunotherapy. Few studies have reported benefit from immunotherapy in EBV positive cancers, and clinical trials investigating the impact of checkpoint inhibitors in EBVaGC are currently underway. This review provides the most recent updates on molecular pathophysiology, epidemiology, clinical features and treatment advances pertaining to EBVaGC.

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Section: Pathophysiology and Tumorigenesismentioning

confidence: 99%

Section: Pathophysiology and Tumorigenesismentioning

confidence: 99%

Outlooks on Epstein-Barr virus associated gastric cancer

Naseem

Barzi

Brezden-Masley

et al. 2018

Cancer Treatment Reviews

171

143

View full text Add to dashboard Cite

show abstract

“…Furthermore, EBVaGC had significant alterations in energy metabolism pathways with down-regulated genes. Wang et al [53] characterized EBVaGC-specific cellular pathways and detected the alterations in macromolecular biosynthetic processes such as carbohydrate, lipid and protein. Deregulation of cholesterol transport and lipoprotein clearance pathways is also evident in EBVaGC [44].…”

Section: Resultsmentioning

confidence: 99%

Bleomycin alters intratumoral immune response of EBV-associated gastric cancer by ENTPD8 and PCOLCE2

Chen

2023

Preprint

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Background EBV-associated gastric cancer (EBVaGC) with high PD-L1 level, is most likely to be the next subgroup benefited from immunotherapy. However, complicated with histological and aetiological heterogeneity, tolerance persists which was usually alleviated by clinical adjuvant chemotherapy (bleomycin). Identifying biomarkers of intratumoral immune response was critical for further understanding the direct mechanism of immunotherapy effectiveness. Method Firstly, to identify gene sets involved in both GC tumorigenesis and EBV infection, a transcriptome sequencing data (GSE51575) was collected for different expression gene (DEG) screening and functional enrichment analysis. Through constructing a prognostic model based on 25 repeated DEGs and evaluating immune correlations subsequently, the influence of ENTPD8 and PCOLCE2 in prognosis and immunotherapy was confirmed. In addition, the binding energy between bleomycin and targets was calculated based on hydrogen bond. Result A total of 572 down- and 162 up-regulated genes in normal tissue vs. GC tissue while 196 down- and 240 up-regulated genes in EBVnGC vs. EBVaGC were detected with logFC ≥ 2 and p-value ≤ 0.05. Among them, ENTPD8 and PCOLCE2 were reduced in EBVaGC which was associated with prognosis significantly and mediated dysregulation of immune response inversely. Besides, the expression trends of ENTPD8 (positive) and PCOLCE2 (negative) were also opposite when binding to bleomycin with the most stable binding energy-4.589 kcal/mol and − 4.025 kcal/mol, respectively. Conclusion Summarily, the improvement of immunotherapy caused by bleomycin as an adjuvant chemotherapy drug may mainly depend on the fluctuation of intratumoral immune response in EBVaGC mediated by the expression of ENTPD8 and PCOLCE2.

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“…The specific programs of viral gene expression found in EBVaGC can target cell signaling pathways leading to increased proliferation, cell survival, immune invasion, augmented epithelial-to-mesenchymal transition (EMT) and acquisition of stemness features [ 15 ]. For instance, Zhao et al reported 13 pathways deregulated in EBVaGC, including mitogen-activated protein kinase (MAPK), Wnt and focal adhesion etc., which could facilitate rapid tumor growth [ 26 , 27 ]. Coincidently, some differential proteins mentioned above were indicated to participate in the genesis of gastric adenocarcinoma or stromal tumors via these classical pathways such as GBP5, C5AR1 and THRAP3 [ 28 – 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…Beyond that, EBVaGC-specific cellular pathways have also been increasingly explored [ 11 ]. For example, Want et al found alterations in macromolecular biosynthetic processes, and deregulation of cholesterol transport and lipoprotein clearance pathways was also evident in EBVaGC [ 26 , 31 ]. Novel findings were observed in our prediction for the biological function of differentially expressed proteins in EBVaGC.…”

Section: Discussionmentioning

confidence: 99%

Identification of differential proteomics in Epstein-Barr virus-associated gastric cancer and related functional analysis

Wang

et al. 2021

Cancer Cell Int

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Background Epstein-Barr virus-associated gastric cancer (EBVaGC) is the most common EBV-related malignancy. A comprehensive research for the protein expression patterns in EBVaGC established by high-throughput assay remains lacking. In the present study, the protein profile in EBVaGC tissue was explored and related functional analysis was performed. Methods Epstein-Barr virus-encoded RNA (EBER) in situ hybridization (ISH) was applied to EBV detection in GC cases. Data-independent acquisition (DIA) mass spectrometry (MS) was performed for proteomics assay of EBVaGC. Functional analysis of identified proteins was conducted with bioinformatics methods. Immunohistochemistry (IHC) staining was employed to detect protein expression in tissue. Results The proteomics study for EBVaGC was conducted with 7 pairs of GC cases. A total of 137 differentially expressed proteins in EBV-positive GC group were identified compared with EBV-negative GC group. A PPI network was constructed for all of them, and several proteins with relatively high interaction degrees could be the hub genes in EBVaGC. Gene enrichment analysis showed they might be involved in the biological pathways related to energy and biochemical metabolism. Combined with GEO datasets, a highly associated protein (GBP5) with EBVaGC was screened out and validated with IHC staining. Further analyses demonstrated that GBP5 protein might be associated with clinicopathological parameters and EBV infection in GC. Conclusions The newly identified proteins with significant differences and potential central roles could be applied as diagnostic markers of EBVaGC. Our study would provide research clues for EBVaGC pathogenesis as well as novel targets for the molecular-targeted therapy of EBVaGC.

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Interpreting the distinct and shared genetic characteristics between Epstein–Barr virus associated and non-associated gastric carcinoma

Cited by 4 publications

References 61 publications

Outlooks on Epstein-Barr virus associated gastric cancer

Outlooks on Epstein-Barr virus associated gastric cancer

Bleomycin alters intratumoral immune response of EBV-associated gastric cancer by ENTPD8 and PCOLCE2

Identification of differential proteomics in Epstein-Barr virus-associated gastric cancer and related functional analysis

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