Analysis of Promoter Methylation, Polymorphism and Expression Prole of Cytotoxic T-Lymphocyte-Associated Antigen-4 in Patients with Gastric Cancer

2014 ◽  
Vol 23 (3) ◽  
pp. 249-253 ◽  
Author(s):  
Dor Mohammad Kordi-Tamandani ◽  
Shahrbbanou Karimi Davani ◽  
Taybeh Baranzehi ◽  
Simin Hemati
Keyword(s):  
Gastric Cancer ◽  
T Cell Activation ◽  
T Lymphocyte ◽  
Promoter Methylation ◽  
Cytotoxic T Lymphocyte ◽  
Methylation Status ◽  
Cancer Tissue ◽  
Tissue Samples ◽  
Increased Risk ◽  
Ctla4 Gene

AbstractBackground & Aim: Cytotoxic T lymphocyte-associated antigen-4 (CTLA4) is a crucial immune-checkpoint receptor regulating T-cell activation. The current study was carried out to evaluate the function of CTLA4 gene in patients with gastric cancer.Methods: The methylation of CTLA4 gene promoter was evaluated by methylation-specific polymerase chain reaction (MSP) technique using 85 paraffin-embedded gastric cancer tissue samples and normal tissue on the tumor margins as control tissue samples. Expression analysis was performed on paraffin-embedded tissue samples (25 each of cancerous and normal tissues) using Real-time PCR.Results: Statistically significant differences were observed between the tumor and margin-cell areas withrespect to promoter methylation status (OR = 4.829, 95% CI: 2.46-9.48, p < 0.001) and CTLA4 expression profile (mean ± SD = 7.56 ± 17.35, p = 0.04).Conclusion: To the best of our knowledge, the current study is the first one highlighting the association between promoter hypermethylation of CTLA4 gene, decreased CTLA4 expression, and increased risk of gastric cancer.

scholarly journals Synergic effect of diabetes mellitus and H. pylori infection on proliferation of cells via downregulating the expression of PTEN by hypermethylating its promoter region

2020 ◽  
Author(s):  
Huibin Lu ◽  
Xinwei Han ◽  
Jianzhuang Ren ◽  
Kewei Ren ◽  
Zongming Li ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gastric Cancer ◽  
Dna Methylation ◽  
Promoter Methylation ◽  
Methylation Status ◽  
Suppressor Gene ◽  
Tissue Samples ◽  
Tumor Tissues ◽  
Pten Mrna ◽  
H Pylori

Abstract Background It has been reported that CagA of H. pylori reduced the expression of PTEN by enhancing its promoter methylation. Furthermore, DM may also promote the methylation status of PTEN, a tumor suppressor gene in Gastric cancer. It is intriguing to explore whether DM may strengthen the tumorigenic effect of HP by promoting the methylation of PTEN promoter and whether the administration of metformin may reduce the risk of GC by suppressing the methylation of PTEN promoter. Methods Bisulfite sequencing PCR was performed to measure the DNA methylation of PTEN promoter in GC patients and HGC-27 cells treated under different conditions. Quantitative real-time PCR was carried out to measure the expression of PTEN mRNA. Immunohistochemistry and Western blot were used to evaluate the expression of PTEN protein. Immunofluorescence and flow cytometry were performed to analyze the apoptosis of GC tissue samples and HGC-27 cells treated under different conditions. MTT assay was carried out to examine the proliferation of HGC-27 cells. Results DNA methylation of PTEN promoter was synergetic enhanced by HP infection and Diabetes mellitus in patients with Gastric cancer. Accordingly, the expression of PTEN was suppressed in GC patients with HP infection and DM. Furthermore, cell apoptosis was decreased in GC patients with HP infection and DM. Metformin showed an apparent effect on maintaining CagA induced elevation of PTEN promoter methylation, thus attenuating the PTEN expression, increasing the proliferation and suppressing the apoptosis of HGC-27 cells. Conclusion In this study, we collected GC tumor tissues from GC patients with or without DM/HP to compare their PTEN methylation and expression while testing the effect of Metformin on the methylation of PTEN promoter. Our study provided evidence for the mechanism underlying the therapeutic role of Metformin in GC treatment.

A PILOT STUDY OF HER-2/NEU GENE AMPLIFICATION ASSESSED BY FLUORESCENCE IN SITU HYBRIDIZATION (FISH) IN GASTRIC CANCER

2014 ◽  
pp. 15-20
Author(s):  
Van Huy Tran ◽  
Thi Minh Thi Ha ◽  
Trung Nghia Van ◽  
Viet Nhan Nguyen ◽  
Phan Tuong Quynh Le ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Cancer Patients ◽  
Gene Amplification ◽  
Cancer Tissue ◽  
Tissue Samples ◽  
Her 2 ◽  
Gastric Cancer Patients

Background: HER-2/neu is a predictive biomarker for treatment of gastric cancer using trastuzumab in combination with chemotherapy. This study aimed to evaluate the status of HER-2/neu gene amplification using fluorescence in situ hybridization (FISH) in gastric cancer. Patients and methods: thirty six gastric cancer patients were assessed HER-2/neu gene amplification by FISH using PathVysionTM HER-2 DNA Probe kit (including HER-2/neu probe and CEP-17 probe) with biopsy and surgical specimens. Results: The HER-2/neu gene amplification was observed in three cases (8.3%), the HER-2/neu gene amplification rate in Lauren’s intestinal-type and diffuse-type were 11.8% and 5.2%, respectively. Conclusion: We applied successfully FISH technique with gastric cancer tissue samples. This technique could be performed as routine test in gastric cancer in order to select patients that benefit from trastuzumab in combination with chemotherapy.

Cytotoxic T‐lymphocyte‐associated protein 4 in gastric cancer: Prognosis and association with PD‐L1 expression

2021 ◽  
Author(s):  
Marina Alessandra Pereira ◽  
Tiago Biachi Castria ◽  
Marcus Fernando Kodama Pertille Ramos ◽  
André Roncon Dias ◽  
Leonardo Cardili ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Cancer Prognosis

Association Between Cyclin D1 Polymorphism with CpG Island Promoter Methylation Status of Tumor Suppressor Genes in Gastric Cancer

2010 ◽  
Vol 55 (12) ◽  
pp. 3449-3457 ◽  
Author(s):  
Tomomitsu Tahara ◽  
Tomoyuki Shibata ◽  
Masakatsu Nakamura ◽  
Hiromi Yamashita ◽  
Daisuke Yoshioka ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Suppressor ◽  
Cyclin D1 ◽  
Promoter Methylation ◽  
Tumor Suppressor Genes ◽  
Cpg Island ◽  
Methylation Status ◽  
Suppressor Genes ◽  
Promoter Methylation Status

The Relationship Between P16INK4A and TP53 Promoter Methylation and The Risk and Prognosis in Patients With Oesophageal Cancer in Thailand

2021 ◽  
Author(s):  
Arisara Poosari ◽  
Thitima Nutravong ◽  
Wises Namwat ◽  
Wiphawan Wasenang ◽  
Prakasit Sa-ngiamwibool ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Oesophageal Cancer ◽  
Promoter Methylation ◽  
Cox Regression ◽  
Methylation Status ◽  
Predictive Biomarker ◽  
Study Data ◽  
Tumour Suppressor Genes ◽  
Promoter Methylation Status ◽  
Increased Risk

Abstract DNA methylation can regulate the expression of tumour suppressor genes P16 and TP53, environmental factors, which are both important factors related to an increased risk and prognosis of oesophageal cancer (EC). However, the association between these two genes methylation status, as well as the effects of gene-environment interactions, EC risk remains unclear. A Hospital-based case-control study data were collected from 105 new EC cases and 108 controls. Promoter methylation status was investigated for P16 and TP53 genes using methylation-specific polymerase (MSP) chain reaction methods with SYBR green. Logistic and Cox regression models were used to analyse the association of P16 and TP53 promotor methylation status with EC risk and prognosis, respectively. Our results suggest P16, TP53 methylation significantly increased the risk of EC (OR = 5.24, 95 % CI: 2.57–10.66, P < 0.001; OR = 3.38, 95% CI: 1.17–6.67, P < 0.001, respectively). In addition, P16 and TP53 promoter methylation status and the combined effects between environmental factors and its methylations in tissue were correlated with the EC risk and prognosis of EC patients. As a new biomarker, the methylation of P16 and TP53 can serve as a potential predictive biomarker of EC.

scholarly journals Induction of Cytotoxic T Lymphocyte Antigen 4 (Ctla-4) Restricts Clonal Expansion of Helper T Cells

2001 ◽  
Vol 194 (7) ◽  
pp. 893-902 ◽  
Author(s):  
Alden M. Doyle ◽  
Alan C. Mullen ◽  
Alejandro V. Villarino ◽  
Anne S. Hutchins ◽  
Frances A. High ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell Activation ◽  
T Lymphocyte ◽  
Cd4 T Cells ◽  
Cell Activation ◽  
Cytotoxic T Lymphocyte ◽  
Clonal Expansion ◽  
Negative Regulator ◽  
Lymphocyte Antigen ◽  
Cell Divisions

Cytotoxic T lymphocyte antigen (CTLA)-4 plays an essential role in immunologic homeostasis. How this negative regulator of T cell activation executes its functions has remained controversial. We now provide evidence that CTLA-4 mediates a cell-intrinsic counterbalance to restrict the clonal expansion of proliferating CD4+ T cells. The regulation of CTLA-4 expression and function ensures that, after ∼3 cell divisions of expansion, most progeny will succumb to either proliferative arrest or death over the ensuing three cell divisions. The quantitative precision of the counterbalance hinges on the graded, time-independent induction of CTLA-4 expression during the first three cell divisions. In contrast to the limits imposed on unpolarized cells, T helper type 1 (Th1) and Th2 effector progeny may be rescued from proliferative arrest by interleukin (IL)-12 and IL-4 signaling, respectively, allowing appropriately stimulated progeny to proceed to the stage of tissue homing. These results suggest that the cell-autonomous regulation of CTLA-4 induction may be a central checkpoint of clonal expansion of CD4+ T cells, allowing temporally and spatially restricted growth of progeny to be dictated by the nature of the threat posed to the host.

Estimation of associations between 10 common gene polymorphisms and gastric cancer: evidence from a meta-analysis

2019 ◽  
Vol 73 (6) ◽  
pp. 318-321
Author(s):  
Zongjing Xie ◽  
Bingmei Wang ◽  
Yongjie Chai ◽  
Junyin Chen
Keyword(s):  
Gastric Cancer ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Meta Analysis ◽  
Interleukin 4 ◽  
East Asians ◽  
Mannose Binding ◽  
Binding Lectin ◽  
Positive Results ◽  
Review Manager

AimsAssociations between polymorphisms in cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)/mannose-binding lectin (MBL)/interleukin-4 (IL-4)/interleukin-6 (IL-6)/phospholipase C ε−1 (PLCE1) and gastric cancer (GC) were already reported by many studies, yet the conclusions of these studies were somehow controversial. The aim of this meta-analysis was to better clarify associations between polymorphisms in CTLA-4/MBL/IL-4/IL-6/PLCE1 and GC by combing the results of all relevant studies.MethodsEligible studies were searched from PubMed, Embase, WOS and CNKI. We used Review Manager to combine the results of individual studies.ResultsForty-three studies were included in this meta-analysis. Combined results revealed that CTLA-4 rs5742909 (dominant comparison: OR: 1.58, 95 % CI: 1.01 to 2.48; allele comparison: OR: 1.69, 95 % CI: 1.12 to 2.56) and PLCE1 rs2274223 (dominant comparison: OR: 0.84, 95 % CI: 0.72 to 0.98; recessive comparison: OR: 1.23, 95 % CI: 1.08 to 1.40; over-dominant comparison: OR: 1.16, 95 % CI: 1.00 to 1.34; allele comparison: OR 0.88, 95 % CI 0.78 to 0.99) polymorphisms were significantly associated with GC in the general population. We also obtained similar significant associations with GC for rs5742909 and rs2274223 polymorphisms in East Asians. Nevertheless, no positive results were observed for the other eight investigated polymorphisms.ConclusionCollectively, this meta-analysis demonstrated that CTLA-4 rs5742909 and PLCE1 rs2274223 polymorphisms may confer susceptibility to GC, especially for East Asians.

scholarly journals Predictive value of the serum RASSF10 promoter methylation status in gastric cancer

2019 ◽  
Vol 47 (7) ◽  
pp. 2890-2900 ◽  
Author(s):  
Yilin Hu ◽  
Peng Ma ◽  
Ying Feng ◽  
Peng Li ◽  
Hua Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Promoter Methylation ◽  
Cox Regression ◽  
Methylation Status ◽  
Disease Free Survival ◽  
Prognostic Indicator ◽  
Chronic Atrophic Gastritis ◽  
Survival Times ◽  
Cox Regression Analysis ◽  
Specific Pcr

Background This study aimed to investigate whether the detection of methylation in the promoter of the Ras association domain family 10 gene ( RASSF10) in the serum of patients with gastric cancer (GC) by methylation-specific PCR (MSP) can be used as a diagnostic and prognostic indicator of GC. Methods We used MSP to examine RASSF10 methylation levels in the serum and/or tumor samples from 100 GC patients, 50 patients with chronic atrophic gastritis (CAG), and 45 healthy controls (HC). We also analyzed clinicopathological and follow-up data. Results Our results showed that the rate of serum RASFF10 promoter methylation among patients with GC (49/100) was higher than in those with CAG (1/50) or HC (0/45). Moreover, the RASSF10 methylation status was consistent between serum and tumor tissues. GC patients with serum RASSF10 promoter methylation had significantly shorter overall survival and disease-free survival times than GC patients without serum RASSF10 promoter methylation. Multivariable Cox regression analysis showed that serum RASSF10 promoter methylation and lymph node metastasis both correlated with reduced survival in GC patients. Conclusions Detection of the serum RASSF10 methylation status by MSP is feasible as a diagnostic and prognostic indicator of GC.

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