Expression and significance of EBV, ARID1A and PIK3CA in gastric carcinoma

Zhou, Huan; Tan, Shengkui; Li, Hong; Lin, Xiangtao

doi:10.3892/mmr.2019.9886

Cited by 16 publications

(17 citation statements)

References 33 publications

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“…The present results suggested that ARID1A and PIK3CA may be associated in the development and progression of GC via a specific mechanism. In particular, the PIK3CA mutation rate has been reported to be associated with GC penetration [16], and ICGC reported Mutations of ARID1A and PIK3CA are known to be mutually exclusive in GC, with similar results in this study. The present results suggested that ARID1A and PIK3CA may be associated in the development and progression of GC via a specific mechanism.…”

Section: Discussionsupporting

confidence: 86%

“…The present results suggested that ARID1A and PIK3CA may be associated in the development and progression of GC via a specific mechanism. In particular, the PIK3CA mutation rate has been reported to be associated with GC penetration [16], and ICGC reported mutation rates of 9.7% in Japanese patients. However, in this study there was no case of PIK3CA mutation.…”

Section: Discussionmentioning

confidence: 99%

“…LRP1 is known to act as a suppressor or promoter of cancer [15][16][17]. In addition, it has already been reported that LRP1 is related to the intracellular autophagy of CagA, which affects the carcinogenesis of GC.…”

Section: Analysis Of Expression Of Lrp1 and Accumulation Of Cagamentioning

confidence: 99%

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Genomic Characterization of Non-Invasive Differentiated-Type Gastric Cancer in the Japanese Population

Nakamura

Urabe

Kagemoto

et al. 2020

Cancers

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Background and aims: Recent genomic characterization of gastric cancer (GC) by sequencing has revealed a large number of cancer-related genes. Research to characterize the genomic landscape of cancer has focused on established invasive cancer to develop biomarkers for therapeutic or diagnostic targets, and nearly all GC reports have been about advanced GC. The aim of this study is to identify recurrently mutated genes in non-invasive GC and, in particular, the driver mutations that are associated with the development of GC. Methods and results: We performed whole-exome sequencing of 19 fresh frozen specimens of differentiated-type non-invasive GC and targeted sequencing for 168 genes of 30 formalin-fixed paraffin-embedded archival specimens of differentiated-type non-invasive GC. We found that TP53 and LRP1 are significantly associated with non-invasive GC. It has been reported that LPR1 is associated with CagA autophagy in gastric mucosa. Therefore, we downloaded RNA sequence data for gastric cancer from the The Cancer Genome Atlas (TCGA) Genomic Data Commons Data Portal and examined the differences in LRP1 gene expression levels. The expression level was significantly lower in cases without LRP1 mutation than in cases with LRP1 mutation. Based on these results, fluorescent immunostaining for CagA was performed for 49 of the above samples to evaluate CagA accumulation within the cancerous tissue. Accumulation of CagA was significantly greater when an LRP1 mutation was present than without a mutation. Conclusion: These data suggest that LRP1 mutation is an important change promoting the transformation of gastric mucosa to GC early in the carcinogenesis of cancer.

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Section: Discussionsupporting

confidence: 86%

“…The present results suggested that ARID1A and PIK3CA may be associated in the development and progression of GC via a specific mechanism. In particular, the PIK3CA mutation rate has been reported to be associated with GC penetration [16], and ICGC reported mutation rates of 9.7% in Japanese patients. However, in this study there was no case of PIK3CA mutation.…”

Section: Discussionmentioning

confidence: 99%

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Genomic Characterization of Non-Invasive Differentiated-Type Gastric Cancer in the Japanese Population

Nakamura

Urabe

Kagemoto

et al. 2020

Cancers

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“…It was also shown that EBV infection is associated with a reduction of the number of CD4 + Tlymphocytes in patients with EBV-related cancer (20). Despite the involvement of EBV infection in the development of cancer having been extensively studied (5,8,9,(21)(22)(23)(24)(25)(26)(27), reports analyzing the initial phase of immune response and lymphocyte activation affected by viral infection are rare. During primary EBV infection, antibodies to VCA IgM are generated and persist from weeks to months.…”

Section: Discussionmentioning

confidence: 99%

T-Lymphocyte Activation Is Correlated With the Presence of Anti-EBV in Patients With Laryngeal Squamous Cell Carcinoma

Klatka

Hymos

Szkatuła-Łupina

et al. 2019

In Vivo

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Background/Aim: Chronic viral infection is an important risk factor in the development of cancer. Failure of immune response to clear the oncogenic infection can facilitate cancer progression. The aim of the present study was to analyze early and late activation of T-lymphocytes related to Epstein-Barr virus (EBV) infection by the expression of markers of activation (CD69, CD25) on the surface of Tlymphocytes (CD3 + , CD4 + , CD8 +) in patients bearing laryngeal cancer according to absence/presence immunoglobulin G antibodies to EBV nuclear antigen (EBNA1). Materials and Methods: Thirty-three patients with laryngeal squamous cell carcinoma (LC) and 20 volunteers without cancer (control group) were enrolled in the study. Peripheral blood samples were collected from every individual. The markers of activation of T-lymphocytes were determined by flow cytometry, whereas commercial immunoenzymatic assay kits were used for detection of anti-viral capsid antigen (VCA) IgM, anti-VCA IgG, and anti-EBNA1 IgG. Results: Increased early activation of CD8 + and CD4 + T-lymphocytes was found in patients with LC. There was a significantly higher proportion of CD4 + and CD8 + T-lymphocytes expressing CD69 antigen in patients with LC compared to the control group. The proportion of CD4 + CD25 + T-lymphocytes in patients with LC positive for anti-EBNA1 IgG and anti-VCA IgM was lower compared to patients without antibodies to VCA IgM. Conclusion: The dysfunction of immune response in larynx cancer patients could be associated with EBV infection.

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“…EBV is a carcinogenic virus, and studies have shown that the expression levels of ARID1A and PIK3CA are closely associated with the depth of GC invasion. As such, PIK3CA mutations in EBV-associated GC are usually accompanied by ARID1A mutations [27]. In the present study, we detected a high frequency of ARID1A and PIK3CA mutations; thus in the future, we intend to investigate the relationship between ARID1A, PIK3CA and EBER, and to analyze the expression of these proteins in GC and adjacent normal tissues.…”

Section: Discussionmentioning

confidence: 56%

Clinicopathological features of Epstein-Barr virus infection, microsatellite instability, tumor mutation burden and PD-L1 status in Chinese patients with gastric cancer

Zhang

Li³

2020

Preprint

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Objectives: Gastric cancer (GC) is the 4th most common type of cancer worldwide. Different GC subtypes exhibit unique molecular features that may potentially guide therapeutic decisions. The aim of the present study was to investigate Epstein-Barr virus (EBV) infection, microsatellite instability (MSI) status, the expression of programmed death-ligand 1 (PD-L1) and gene mutations in patients with surgically-treated GC. Methods: The data of 2,504 GC patients, who underwent potentially curative gastrectomy with lymphadenectomy at Peking University Cancer Hospital between 2013 and 2018, were reviewed from a prospectively collected medical database. We also analyzed the clinicopathological factors associated with the immunohistochemistry (IHC) profiles of these patients, and genetic alterations were analyzed using next generation sequencing (NGS). Results: Mismatch repair-deficient (d-MMR) GC patients were found to have a higher probability of expressing PD-L1 (p<0.001, PD-L1 cutoff value = 1%). In addition, 4 and 6.9% of the 2,504 gastric cancer patients were EBV-positive and d-MMR, respectively. The number of MLH1/PMS2-negative cases was 126 (6%), and the number of MSH2/MSH6-negative cases was 14 (0.9%). d-MMR status was associated with a diffuse/mixed group (p<0.05), but not with tumor differentiation. Furthermore, MSI and d-MMR GC status (detected by NGS and IHC, respectively) were consistently high, and the rate of MSI was higher in patients with d-MMR GC. A number of genes associated with DNA damage repair were detected in GC patients with MSI, including POLE, ETV6, BRCA and RNF43. In patients with a high tumor mutation burden, the most significantly mutated genes were LRP1B (79.07%), ARID1A (74.42%), RNF43 (69.77%), ZFHX3 (65.12%), TP53 (58.14%), GANS (51.16%), BRCA2 (51.16%), PIK3CA (51.16%), NOTCH1 (51.16%), SMARCA4 (48.84%), ATR (46.51%), POLE (41.86%) and ATM (39.53%). Conclusions: Using IHC and NGS, MSI status, protein expression, TMB and genetic alterations were identified in patients with GC, which provides a theoretical basis for the future clinical treatment of GC.

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Expression and significance of EBV, ARID1A and PIK3CA in gastric carcinoma

Cited by 16 publications

References 33 publications

Genomic Characterization of Non-Invasive Differentiated-Type Gastric Cancer in the Japanese Population

Genomic Characterization of Non-Invasive Differentiated-Type Gastric Cancer in the Japanese Population

T-Lymphocyte Activation Is Correlated With the Presence of Anti-EBV in Patients With Laryngeal Squamous Cell Carcinoma

Clinicopathological features of Epstein-Barr virus infection, microsatellite instability, tumor mutation burden and PD-L1 status in Chinese patients with gastric cancer

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