• Journal of Gastric Cancer
• /
• v.5 no.3 s.19
• /
• pp.180-185
• /
• 2005

Purpose: Among tumor-associated antigens, MAGE (melanoma antigen) was named as cancer/testis specific antigens because they are detected exclusively in the testis or cancer cells, including gastric carcinomas. Due to the elicitation of autoimmunitiy to tumors by these antigens either in vitro or in vivo and their tumor specificity, these antigens, thus, appear to be potential targets for tumor-specific immunotherapy. Materials and Methods: The fresh tumor tissue and normal gastric tissue samples were obtained from resected surgical specimens in 53 patients with gastric carcinomas. From the obtained cells, total cellular mRNA was extracted, and RT-PCR and nested PCR were run in 30 and 35 cycles respectively, with two different kinds of primers specially designed to detect six subtypes of MAGE DNA simultaneously. Results: In the 53 normal tissue, there was no expression of MAGE, but in the 53 cancer tissues, MAGE was expressed in 13 tissues (24.5%). Our data did not exhibit any correlation with the expression of the MAGE gene and clinicopathological factors. Conclusion: In our data, since 24.5% of gastric cancer tissues expressed MAGE, it should become possible to immunize a significant proportion of patients with advanced gastric carcinomas against the antigens encoded by these genes, provided that more antigenic peptides encoded by the genes of the MAGE family can be identified in the near future. (J Korean Gastric Cancer Assoc 2005;5:180-185)

• Journal of Preventive Medicine and Public Health
• /
• v.49 no.2
• /
• pp.97-107
• /
• 2016

Objectives: Research on how the risk of gastric cancer increases with Epstein-Barr virus (EBV) infection is lacking. In a systematic review that investigated studies published until September 2014, the authors did not calculate the summary odds ratio (SOR) due to heterogeneity across studies. Therefore, we include here additional studies published until October 2015 and conduct a meta-analysis with meta-regression that controls for the heterogeneity among studies. Methods: Using the studies selected in the previously published systematic review, we formulated lists of references, cited articles, and related articles provided by PubMed. From the lists, only case-control studies that detected EBV in tissue samples were selected. In order to control for the heterogeneity among studies, subgroup analysis and meta-regression were performed. Results: In the 33 case-control results with adjacent non-cancer tissue, the total number of test samples in the case and control groups was 5280 and 4962, respectively. In the 14 case-control results with normal tissue, the total number of test samples in case and control groups was 1393 and 945, respectively. Upon meta-regression, the type of control tissue was found to be a statistically significant variable with regard to heterogeneity. When the control tissue was normal tissue of healthy individuals, the SOR was 3.41 (95% CI, 1.78 to 6.51; I-squared, 65.5%). Conclusions: The results of the present study support the argument that EBV infection increases the risk of gastric cancer. In the future, age-matched and sex-matched case-control studies should be conducted.

• Proceedings of the Korean Society for Bioinformatics Conference
• /
• 2005.09a
• /
• pp.366-370
• /
• 2005

Tissue microarry is one of the high throughput technologies in the post-genomic era. Using tissue microarray, the researchers are able to investigate large amount of gene expressions at the level of DNA, RNA, and protein The important aspect of tissue microarry is its ability to assess a lot of biomarkers which have been used in clinical practice. To manipulate the categorical data of tissue microarray, we applied Bayesian network classifier algorithm. We identified that Bayesian network classifier algorithm could analyze tissue microarray data and integrating prior knowledge about gastric cancer could achieve better performance result. The results showed that relevant integration of prior knowledge promote the prediction accuracy of survival status of the immunohistochemical tissue microarray data of 18 tumor suppressor genes. In conclusion, the application of Bayesian network classifier seemed appropriate for the analysis of the tissue microarray data with clinical information.

• Journal of Gastric Cancer
• /
• v.18 no.4
• /
• pp.356-367
• /
• 2018

Purpose: Kallikrein (KLK) proteases are hormone-like signaling molecules with critical functions in different cancers. This study investigated the expression of KLK6 in gastric cancer and its potential role in the growth, migration, and invasion of gastric cancer cells. Materials and Methods: In this study, we compared protein levels of KLK6, vascular endothelial growth factor (VEGF), and matrix metallopeptidase (MMP) 9 in normal gastric epithelial and gastric cancer cell lines by western blot. Fluorescence-activated cell sorting was employed to sort 2 clones of SGC-7901 cells with distinct KLK6 expression, namely, KLK6-high ($KLK6^{high}$) and KLK6-low ($KLK6^{low}$), which were then expanded. Lastly, immunohistochemical analysis was performed to investigate KLK6 expression in gastric cancer patients. Results: The expression levels of KLK6, VEGF, and MMP 9, were significantly higher in the gastric cancer cell lines SGC-7901, BGC-823, MKN-28, and MGC-803 than in the normal gastric epithelial cell line GES-1. Compared to $KLK6^{low}$ cells, $KLK6^{high}$ cells showed enhanced viability, colony-forming ability, migration, and invasion potential in vitro. Importantly, immunohistochemical analysis of a human gastric cancer tissue cohort revealed that the staining for KLK6, VEGF, and MMP9 was markedly stronger in the cancerous tissues than in the adjacent normal tissues. KLK6 expression also correlated with that of VEGF and MMP9 expression, as well as several key clinicopathological parameters. Conclusions: Together, these results suggest an important role for KLK6 in human gastric cancer progression.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.8
• /
• pp.3523-3525
• /
• 2015

Gastric cancer is the second most common cause of cancer death worldwide. Environmental as well as genetic factors have been shown to be involved in its genesis. Among genetic factors, loss of function of a tumor suppressive gene named promyelocytic leukemia (PML) has been demonstrated in gastric cancer. In order to cast light in the mechanism by which PML protein is under-expressed in gastric cancer cells, we analyzed all exons and intron-exon boundaries of PML gene in 50 formalin-fixed paraffin-embedded tissue blocks from gastric carcinoma tumors by means of PCR-SSCP and CSGE, with direct sequencing of abnormally shifted bands. We found a novel sequence variant of unknown significance localized in intron 5 in 3 samples (c.1398+84delA). We did not detect any deleterious mutations of the PML gene. This study shows that PML mutations may not contribute to gastric adenocarcinoma development. Post-translational modifications or protein degradation might be mechanisms by which PML is not expressed in gastric tumors.

• Molecules and Cells
• /
• v.41 no.6
• /
• pp.591-602
• /
• 2018

Gastric cancer is the fifth most common type of malignancy worldwide, and the survival rate of patients with advanced-stage gastric cancer is low, even after receiving chemotherapy. Here, we validated neurotensin receptor 1 (NTSR1) as a potential therapeutic target in gastric cancer. We compared NTSR1 expression levels in sixty different gastric cancer-tissue samples and cells, as well as in other cancer cells (lung, breast, pancreatic, and colon), by assessing NTSR1 expression via semi-quantitative real-time reverse transcription polymerase chain reaction, immunocytochemistry and western blot. Following neurotensin (NT) treatment, we analyzed the expression and activity of matrix metalloproteinase-9 (MMP-9) and further determined the effects on cell migration and invasion via wound-healing and transwell assays. Our results revealed that NTSR1 mRNA levels were higher in gastric cancer tissues than non-cancerous tissues. Both of NTSR1 mRNA levels and expression were higher in gastric cancer cell lines relative to levels observed in other cancer-cell lines. Moreover, NT treatment induced MMP-9 expression and activity in all cancer cell lines, which was significantly decreased following treatment with the NTSR1 antagonist SR48692 or small-interfering RNA targeting NTSR1. Furthermore, NT-mediated metastases was confirmed by observing epithelial-mesenchymal transition markers SNAIL and E-cadherin in gastric cancer cells. NT-mediated invasion and migration of gastric cancer cells were reduced by NTSR1 depletion through the Erk signaling. These findings strongly suggested that NTR1 constitutes a potential therapeutic target for the inhibition of gastric cancer invasion and metastasis.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.7
• /
• pp.4239-4242
• /
• 2013

It is reported that the expression level of MLL3 in gastric cancer tissue highly correlates with tumor progression. However, whether MLL3 genetic variants are associated with the risk of gastric cancer remains unclear. In this study, we conducted a genotyping analysis for MLL3 in 314 cases of gastric cancer and 322 controls from the Chinese Han population. 4 SNPs (rs6943984, rs4725443, rs3800836, rs6464211) were selected for the present analysis. We found 2 SNPs (rs6943984, rs4725443) of MLL3 gene were significantly associated with the risk of gastric cancer : the rs6943984 with the minor allele A and rs4725443 with the minor allele C revealed strong associations with increased gastric cancer risk [P < 0.001, OR=1.97, 95% CI=1.48~2.64 and P <0.001, OR=2.23, 95% CI=1.54~3.24]. Haplotype analysis of the four SNPs showed that haplotype A-T-A-C, G-T-G-C, and G-C-A-C increased the risk of gastric cancer (P <0.001, P=0.18, and P<0.001, respectively), while haplotype G-T-A-C significantly reduced the risk of gastric cancer (P <0.001). We concluded that MLL3 variants are significantly associated with gastric cancer risk. Our results for the first time provided new insight into susceptibility factors of MLL3 gene variants in carcinogenesis of gastric cancer of the Chinese Han population.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.10
• /
• pp.5713-5718
• /
• 2013

Background: DNA methyltransferase-3a (DNMT3a) plays significant roles in embryogenesis and the generation of aberrant methylation in carcinogenesis. This study aimed to investigate associations between single nucleotide polymorphisms (SNPs) of the DNMT3a gene and risk of Helicobacter pylori infection, gastric atrophy and gastric cancer. Methods: The subjects comprised 447 patients with gastric cancer; 111 individuals with gastric atrophy and 961 healthy controls. Two SNPs (rs1550117 and rs13420827) of the DNMT3a gene were genotyped by Taqman assay. DNMT3a expression was analyzed in cancer tissues from 89 patients by tissue microarray technique. Odds ratio (ORs) and 95% confidence intervals were calculated by multivariate logistic regression. Results: Among healthy controls, risk of H.pylori infection was significantly higher in subjects with the rs1550117 AA genotype, compared to those with GG/AG genotypes of DNMT3a [OR=2.08, (95%CI: 1.02-4.32)]. However, no significant correlation was found between the two SNPs and risk of developing gastric atrophy or gastric cancer. In addition, no increase in DNMT3a expression was observed in the gastric cancer with H.pylori infection. Conclusions: This study revealed that DNMT3a rs1550117 polymorphism is significantly associated with an increased risk of H. pylori infection, but did not support any evidence for contributions of DNMT3a rs1550117 and rs13420827 to either gastric atrophy or gastric cancer. The biological roles of DNMT3a polymorphisms require further investigation.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.6
• /
• pp.2833-2836
• /
• 2012

Aim: Gastric cancer is the third most frequent cause of cancer mortality worldwide. In Iran, it is one of the leading causes at the national level. Localized at chromosome 8q22, the human MTDH gene has been reported to be over-expressed in a spectrum of malignancies. However, since there is a lack of data concerning with expression in gastric cancer at the transcriptional level, in this study we evaluated MTDH expression in Iranian cases. Methods: Totally, thirty paired gastric samples were examined by quantitative real-time RT-PCR. Results: Although the mRNA expression was significantly elevated in 46.6% of the examined tumor tissues; its expression was low in others (36.6%). Moreover, there was only a marginal statistical difference between the MTDH gene expression of all tumor specimens compared to their paired non-tumor ones and no statistically significant association with the grades and types of the tumors. Conclusion: Taken together, our results demonstrated that expression of MTDH at the transcriptional level may be increased in gastric cancer tissue samples but with considerable heterogeneity. Due to this, it may have the potential to be used as a target for diagnostic/therapeutic purposes only in a subset of patients.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.3
• /
• pp.1369-1372
• /
• 2016

Background: Platinum compounds are the main drugs for treatment of advanced gastric cancer. Previous studies have shown that clinical outcome with platinum-based compounds depends on ERCC1 polymorphisms. The aim of this study was to investigate the frequency of a common polymorphism of ERCC1 gene (C8092A) in Iranian patients with advanced gastric cancer receiving platinum chemotherapy. Materials and Methods: Genetic analysis of the ERCC1 C8092A polymorphism was performed by the PCR - RFLP method using 50 paraffin-embedded tissue specimens. Results: Of the 50 cases, 32% of individuals showed CC genotype, 24% of them had CA genotype and 44% of patients had AA genotype. Conclusions: Based on the results, using of platinum-based chemotherapy would be expected to be specifically beneficial in only 32% of patients.