Association of single nucleotide polymorphism rs2065955 of the filaggrin gene with susceptibility to Epstein-Barr virus-associated gastric carcinoma and EBV-negative gastric carcinoma

Kuang, Xiaojing; Sun, Lingling; Liu, Shuzhen; Zhao, Zhenzhen; Zhao, Danrui; Liu, Song; Luo, Bing

doi:10.1007/s12250-016-3721-9

Cited by 6 publications

(4 citation statements)

References 39 publications

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“…The genotype AA of rs3126085 (c.3321delA), as a most popular FLG mutation in Chinese Han people, was considered as a hazardous sign for EBV-associated gastric carcinoma ( Yang et al, 2017 ). Another study detected the FLG rs2065955 genotype and allele distribution in 64 EBV-associated gastric carcinoma samples, and found genotype CC may contribute more to the risk of developing EBVaGC ( Kuang et al, 2016 ). Nevertheless, no significant difference in FLG expression was detected by immunohistochemical analysis in those studies.…”

Section: Resultsmentioning

confidence: 99%

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Association of FLG mutation with tumor mutation load and clinical outcomes in patients with gastric cancer

Liu

Tian

et al. 2022

Front. Genet.

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Background: Stomach adenocarcinoma (STAD) is one of the most frequently diagnosed cancers in the world with a poor prognosis due to genetic heterogeneity. The present study aimed to explore potential prognostic predictors and therapeutic targets that can be used for STAD treatment.Methods: We collected relevant data of STAD patients from the Cancer Genome Atlas (TCGA), including somatic mutation, transcriptome, and survival data. We performed a series of analyses such as tumor mutational burden (TMB), immune infiltration, and copy number variation (CNV) analysis to evaluate the potential mechanism of filaggrin (FLG) mutation in gastric cancer. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and gene set enrichment analysis (GSEA) were performed for annotation of differentially expressed genes (DEGs). The STRING online database was used to construct the protein–protein interaction (PPI) and ceRNA network and hub genes were identified. Univariate and multivariate Cox regression analyses were used to determine the effect of selected DEGs on tumor prognosis.Results: The FLG-mutant group (FLG-MT) showed a higher mutation load and immunogenicity in gastric cancer. GO and KEGG analyses identified and ranked unique biologic processes and immune-related pathway maps that correlated with the FLG-mutant target. GSEA analysis showed that several tumorigenesis and metastasis-related pathways were indeed enriched in FLG-mutant tumor tissue. Both cell cycle–related pathways and the DNA damage and repair associated pathways were also enriched in the FLG-MT group. The FLG mutations resulted in increased gastric cancer sensitivity to 24 chemotherapeutic drugs. The ceRNA network was established using Cytoscape and the PPI network was established in the STRING database. The results of the prognostic information further demonstrated that the OS and DFS were significantly higher in FLG mutation carriers, and the FLG gene mutation might be a protective factor.Conclusion: The multiple molecular mechanisms of the FLG gene in STAD are worthy of further investigation and may reveal novel therapeutic targets and biomarkers for STAD treatment.

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Section: Resultsmentioning

confidence: 99%

“…These keratinocytes act as a matrix in the stratum corneum. A previous study has shown that FLG gene mutations possibly bring about a greater susceptibility to Epstein–Barr virus (EBV)–associated gastric carcinoma ( Kuang et al, 2016 ). This may be related to the fact that about 9% of gastric cancers harbor EBV infection.…”

Section: Introductionmentioning

confidence: 99%

Association of FLG mutation with tumor mutation load and clinical outcomes in patients with gastric cancer

Liu

Tian

et al. 2022

Front. Genet.

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“…In a targeted gene approach study, a comparison of 30 EBV+ cases to 120 EBV-negative cases revealed an association for promoter polymorphisms at the TNF-α and IL-10 gene loci [ 201 ]. Additional targeted approach studies revealed associations with Filaggrin (FLG), a filament-associated protein that binds to keratin fibers, in EBV+ GC, and EBV-negative GC [ 202 ]. Glypican-4 (GPC4), a member of the heparan sulphate proteoglycan family, was associated with EBV+ GC [ 203 ].…”

Section: Susceptibility To Ebv-associated Malignanciesmentioning

confidence: 99%

The Microenvironment in Epstein–Barr Virus-Associated Malignancies

et al. 2018

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The Epstein–Barr virus (EBV) can cause a wide variety of cancers upon infection of different cell types and induces a highly variable composition of the tumor microenvironment (TME). This TME consists of both innate and adaptive immune cells and is not merely an aspecific reaction to the tumor cells. In fact, latent EBV-infected tumor cells utilize several specific mechanisms to form and shape the TME to their own benefit. These mechanisms have been studied largely in the context of EBV+ Hodgkin lymphoma, undifferentiated nasopharyngeal carcinoma, and EBV+ gastric cancer. This review describes the composition, immune escape mechanisms, and tumor cell promoting properties of the TME in these three malignancies. Mechanisms of susceptibility which regularly involve genes related to immune system function are also discussed, as only a small proportion of EBV-infected individuals develops an EBV-associated malignancy.

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“…SNPs have been the focus of much interest and debate in recent years regarding their possible role in the development of various types of cancer (Wu et al, 2013). It is widely accepted that the signifi cant SNPs can be used as biomarkers for diagnosis and to evaluate the risk and prognosis of some diseases including cancers (Pipan et al, 2015;Xu et al, 2015;Kuang et al, 2016). However, there is little information available in literature about PPP1R15A gene polymorphism.…”

Section: Introductionmentioning

confidence: 99%

Relationship between PPP1R15A gene polymorphism (rs611251) and Epstein-Barr virus-associated tumors

Song¹,

Liu²,

Zhao³

et al. 2017

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Protein phosphatase 1, regulatory subunit 15A (PPP1R15A), also known as growth arrest and DNA damage-inducible protein GADD34, plays a vital role in promoting cell death and the unfolded protein response (UPR). In order to explore whether the SNP (rs611251) of PPP1R15A gene has a role in different types of Epstein-Barr virus (EBV) - associated tumors, we detected the PPP1R15A gene rs611251 polymorphism in 195 cases of EBV positive tumors (93 lymphomas, 48 gastric carcinomas, 54 nasopharyngeal carcinomas), 208 cases of EBV-negative tumors (136 gastric carcinoma, 19 nasopharyngeal carcinomas, 53 lymphomas) and 113 peripheral blood samples from healthy individuals. Compared with normal controls, the wild type TT and allele T of rs611251 showed higher frequency in gastric carcinoma (GCs), nasopharyngeal carcinomas (NPCs) and lymphomas. However, there was no significant difference between EBV-associated gastric (EBVaGC) and EBVnGC, EBV-positive NPCs and EBV-negative NPCs, EBV-related lymphomas and EBV-negative lymphomas in rs611251 of PPP1R15A. In conclusion, the PPP1R15A rs611251 polymorphism was significantly related to three kinds of tumors. Nevertheless, EBV has no obvious effect on PPP1R15A rs611251 polymorphism of NPC, GC and lymphoma. What's more, the genotype TT and allele T could be risk factors for NPC, GC and lymphoma. Our study explores the relationship between PPP1R15A gene polymorphism (rs611251) and Epstein-Barr virus-associated tumors for the first time. PPP1R15A gene SNP (rs611251) have association with multiple tumor types, which may provide some new clues to the detection and treatment of tumors.

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Association of single nucleotide polymorphism rs2065955 of the filaggrin gene with susceptibility to Epstein-Barr virus-associated gastric carcinoma and EBV-negative gastric carcinoma

Cited by 6 publications

References 39 publications

Association of FLG mutation with tumor mutation load and clinical outcomes in patients with gastric cancer

Association of FLG mutation with tumor mutation load and clinical outcomes in patients with gastric cancer

The Microenvironment in Epstein–Barr Virus-Associated Malignancies

Relationship between PPP1R15A gene polymorphism (rs611251) and Epstein-Barr virus-associated tumors

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