scholarly journals Diffuse Gastric Cancer: A Summary of Analogous Contributing Factors for Its Molecular Pathogenicity

2018 ◽  
Vol 19 (8) ◽  
pp. 2424 ◽  
Author(s):  
Shamshul Ansari ◽  
Boldbaatar Gantuya ◽  
Vo Tuan ◽  
Yoshio Yamaoka
Keyword(s):  
Gastric Cancer ◽  
Diffuse Gastric Cancer ◽  
Cell Integrity ◽  
Diffuse Type ◽  
Asian Countries ◽  
Contributing Factors ◽  
Incidence And Mortality ◽  
Genetic Abnormalities ◽  
H Pylori ◽  
Diffuse Type Gastric Cancer

Gastric cancer is the third leading cause of cancer-related deaths and ranks as the fifth most common cancer worldwide. Incidence and mortality differ depending on the geographical region and gastric cancer ranks first in East Asian countries. Although genetic factors, gastric environment, and Helicobacter pylori infection have been associated with the pathogenicity and development of intestinal-type gastric cancer that follows the Correa’s cascade, the pathogenicity of diffuse-type gastric cancer remains mostly unknown and undefined. However, genetic abnormalities in the cell adherence factors, such as E-cadherin and cellular activities that cause impaired cell integrity and physiology, have been documented as contributing factors. In recent years, H. pylori infection has been also associated with the development of diffuse-type gastric cancer. Therefore, in this report, we discuss the host factors as well as the bacterial factors that have been reported as associated factors contributing to the development of diffuse-type gastric cancer.

scholarly journals Estrogen Aggravates Tumor Growth in a Diffuse Gastric Cancer Xenograft Model

2021 ◽  
Vol 27 ◽  
Author(s):  
Sunyi Lee ◽  
Kyoung Mee Kim ◽  
Seung Yeon Lee ◽  
Joohee Jung
Keyword(s):  
Gastric Cancer ◽  
Tumor Growth ◽  
Rna Sequencing ◽  
Xenograft Model ◽  
Diffuse Gastric Cancer ◽  
Diffuse Type ◽  
Female Mice ◽  
Exogenous Estrogen ◽  
Endogenous Estrogen ◽  
Diffuse Type Gastric Cancer

Gastric cancer has the fifth-highest incidence rate and is the third leading cause of cancer-related deaths worldwide. The incidence of gastric cancer is higher in men than in women, but for the diffuse types of gastric cancer, the trend is opposite. Estrogen is considered the prime culprit behind these differences. Nevertheless, the action of estrogen in gastric cancers remains unclear. In this study, we investigated the effect of estrogen on diffuse-type gastric cancer. Human female diffuse gastric cancer SNU-16 cells were transplanted into male and female mice to analyze the effect of endogenous estrogen on tumor growth. Furthermore, the effect of exogenous estrogen was evaluated in ovariectomized mice. Expressed genes were compared between female and male xenograft models using RNA sequencing analysis. Furthermore, human gene expression omnibus databases were utilized to examine the effect of our target genes on overall survival. SNU-16-derived tumor growth was faster in female mice than in male mice. In total RNA sequencing, interferon gamma receptor 2 (IFNGR2), IQ motif containing E (IQCE), transient receptor potential cation channel subfamily M member 4 (TRPM4), and structure-specific endonuclease subunit SLX4 (SLX4) were found. These genes could be associated with the tumor growth in female diffuse-type gastric cancer which was affected by endogenous estrogen. In an ovariectomized gastric cancer xenograft model, exogenous estrogen promoted tumor growth. Especially, our results indicated that estrogen induced G protein-coupled estrogen receptor expression in these mice. These results suggest that estrogen aggravates tumor progression in female diffuse gastric cancer.

scholarly journals Helicobacter pylori and gastric cancer

2003 ◽  
Vol 11 (4) ◽  
pp. 233-237 ◽  
Author(s):  
Marica Otasevic ◽  
Aleksandar Nagorni ◽  
Dobrila Stankovic-Djordjevic ◽  
Marina Dinic ◽  
Ljiljana Otasevic
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Treatment Group ◽  
Intestinal Type ◽  
Fisher Exact Test ◽  
Diffuse Type ◽  
Exact Test ◽  
Significant Difference ◽  
H Pylori ◽  
Diffuse Type Gastric Cancer

BACKGROUND: Helicobacter pylori (H. pylori) is classified as a Group 1 carcinogen, because H. pylori infection considerably increases the risk of gastric cancer development. METHODS: The study involved a total of 191 patients divided into two groups. The first group comprised 117 patients who underwent endoscopy. A total of 203 biopsy specimens of the gastric mucosa were taken and analyzed using microbiological and histopathological methods. The second group comprised 74 patients with gastric cancer, who were examined for the gastric cancer type, the presence of H. pylori infection and the cancer localization. The presence of H. pylori infection in the tissue was con?firmed by staining pathohistological sections according to the method of Warthin-Starry. The microbilogical diagnosis involved the staining of direct tissue smears according to the method of Gram, as well as the cultivation of the specimens. To test the hypothesis for possible differences in H. pylori positive findings between the treatment groups, x2 test with Yates correction or Fisher exact test were used. RESULTS: The first treatment group comprised 117 patients with various clinical diagnoses. Gastric cancer was diagnosed in 8 patients, and of these 87.50% were found to have H. pylori. No statistically significant difference in H. pylori positive tests was detected between the patients with gastric ulcer and the patients with gastric cancer (Fisher exact test: p=1.00; p>0.05) nor was it established between the patients with duodenal ulcer and those with gastric cancer (Fisher exact test: p= 1.00; p>0.05). The second treatment group comprised 74 patients, of whom 52 (70.27%) had intestinal-type gastric cancer and 22 (29.72%) had diffuse-type gastric cancer. No statistically significant difference in the positive tests for H. pylori was registered between the patients with intestinal-type and those with diffuse-type gastric cancer (x2=0.07; p=0.798; p>0.05). The most frequent localization of the cancer was the antrum. CONCLUSION: The results are supportive of the hypothesis on a correlation between H. pylori infection and gastric adenocarcinoma development, but no differences between the intestinal and diffuse type of adenocarcinoma have been revealed with respect to the malignant process.

scholarly journals Risk of gastric cancer in the second decade of follow-up after Helicobacter pylori eradication

2019 ◽  
Vol 55 (3) ◽  
pp. 281-288 ◽  
Author(s):  
Susumu Take ◽  
Motowo Mizuno ◽  
Kuniharu Ishiki ◽  
Chiaki Kusumoto ◽  
Takayuki Imada ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Incidence Rate Ratio ◽  
Gastric Atrophy ◽  
Diffuse Type ◽  
Gastric Cancer Risk ◽  
Helicobacter Pylori Eradication ◽  
H Pylori ◽  
Diffuse Type Gastric Cancer

Abstract Background and aims Eradication of Helicobacter pylori reduces the risk of gastric cancer. In this study, we investigated the risk beyond 10 years after eradication of H. pylori. Methods We conducted a retrospective cohort study of 2737 patients who had yearly endoscopic follow-up after cure of H. pylori infection. For comparison of gastric cancer risk in the second decade of follow-up with that in the first decade, we calculated standardized incidence ratios (SIRs) by dividing the number of observed cases of gastric cancer in the second decade of follow-up by that of expected cases which was estimated using the incidence rate ratio of age in the first decade. Results During the follow-up for as long as 21.4 years (mean 7.1 years), gastric cancer developed in 68 patients (0.35% per year). The SIRs for diffuse-type gastric cancer was infinity (0 expected case and 4 observed cases) in patients with mild gastric mucosal atrophy and 10.9 (95% confidence interval 4.53–26.1) with moderate atrophy, whereas no significant increase of SIRs was observed in intestinal-type cancer regardless of the grade of baseline gastric atrophy or in diffuse-type cancer in patients with severe atrophy even though who had the highest risk. Conclusions The longer the follow-up, the greater the risk of developing diffuse-type gastric cancer becomes in patients with mild-to-moderate gastric atrophy at baseline. Endoscopic surveillance should be continued beyond 10 years after cure of H. pylori irrespective of the severity of gastric atrophy.

scholarly journals NOD1 rs2075820 (p.E266K) polymorphism is associated with gastric cancer among individuals infected with cagPAI-positive H. pylori

2021 ◽  
Vol 54 (1) ◽  
Author(s):  
Patricio Gonzalez-Hormazabal ◽  
Diana Pelaez ◽  
Maher Musleh ◽  
Marco Bustamante ◽  
Juan Stambuk ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Intestinal Type ◽  
Diffuse Type ◽  
Pathogen Recognition Receptors ◽  
H Pylori ◽  
Gastric Cancer Patients ◽  
Diffuse Type Gastric Cancer ◽  
Allele Model ◽  
Control Study ◽  
Oligomerization Domain

Abstract Background Helicobacter pylori is detected by pathogen recognition receptors including toll-like receptors (TLR) and nucleotide-binding oligomerization domain (NOD)-like receptors, eliciting an innate immune response against this bacteria. The aim of this study was to assess if polymorphisms of TLR2, TLR4, TLR5, NOD1 and NOD2 genes are associated with gastric cancer, in particular in individuals infected with H. pylori. Results A case-control study of 297 gastric cancer patients and 300 controls was performed to assess the association of 17 polymorphisms. Analyses performed under the allele model did not find association with gastric cancer. However, NOD1 rs2075820 (p.E266K) showed association with intestinal-type gastric cancer among H. pylori infected subjects (OR = 2.69, 95% CI 1.41–5.13, p = 0.0026). The association was not statistically significant in diffuse-type gastric cancer cases (OR = 1.26, 95% CI 0.63–2.52, p = 0.51). When the analyses were performed in patients carrying H. pylori strains harboring the cag pathogenicity island (cagPAI), we noticed significant association with NOD1 rs2075820 (OR = 4.90, 95% CI 1.80–3.36, p = 0.0019), in particular for intestinal-type gastric cancer cases (OR = 7.16, 95% CI 2.40–21.33, p = 4.1 × 10− 4) but not among diffuse-type gastric cancer cases (OR = 3.39, 95% CI 1.13–0.10, p = 0.03). Conclusions NOD1 rs2075820 increases the risk of intestinal-type gastric cancer among individuals infected with H. pylori, particularly in those harboring the cagPAI.

scholarly journals Molecular Network Profiling in Intestinal- and Diffuse-Type Gastric Cancer

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3833
Author(s):  
Shihori Tanabe ◽  
Sabina Quader ◽  
Ryuichi Ono ◽  
Horacio Cabral ◽  
Kazuhiko Aoyagi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Drug Resistance ◽  
Signaling Pathways ◽  
Pathway Analysis ◽  
Rna Binding ◽  
Binding Protein ◽  
Diffuse Type ◽  
Mesenchymal Transition ◽  
Diffuse Type Gastric Cancer

Epithelial-mesenchymal transition (EMT) plays an important role in the acquisition of cancer stem cell (CSC) feature and drug resistance, which are the main hallmarks of cancer malignancy. Although previous findings have shown that several signaling pathways are activated in cancer progression, the precise mechanism of signaling pathways in EMT and CSCs are not fully understood. In this study, we focused on the intestinal and diffuse-type gastric cancer (GC) and analyzed the gene expression of public RNAseq data to understand the molecular pathway regulation in different subtypes of gastric cancer. Network pathway analysis was performed by Ingenuity Pathway Analysis (IPA). A total of 2815 probe set IDs were significantly different between intestinal- and diffuse-type GC data in cBioPortal Cancer Genomics. Our analysis uncovered 10 genes including male-specific lethal 3 homolog (Drosophila) pseudogene 1 (MSL3P1), CDC28 protein kinase regulatory subunit 1B (CKS1B), DEAD-box helicase 27 (DDX27), golgi to ER traffic protein 4 (GET4), chromosome segregation 1 like (CSE1L), translocase of outer mitochondrial membrane 34 (TOMM34), YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), ribonucleic acid export 1 (RAE1), par-6 family cell polarity regulator beta (PARD6B), and MRG domain binding protein (MRGBP), which have differences in gene expression between intestinal- and diffuse-type GC. A total of 463 direct relationships with three molecules (MYC, NTRK1, UBE2M) were found in the biomarker-filtered network generated by network pathway analysis. The networks and features in intestinal- and diffuse-type GC have been investigated and profiled in bioinformatics. Our results revealed the signaling pathway networks in intestinal- and diffuse-type GC, bringing new light for the elucidation of drug resistance mechanisms in CSCs.

scholarly journals Identification of a molecular signature of prognostic subtypes in diffuse-type gastric cancer

2019 ◽  
Vol 23 (3) ◽  
pp. 473-482 ◽  
Author(s):  
Seon-Kyu Kim ◽  
Hee-Jin Kim ◽  
Jong-Lyul Park ◽  
Haejeong Heo ◽  
Seon-Young Kim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tissue Microarray ◽  
Microarray Analysis ◽  
Cox Regression ◽  
Molecular Signature ◽  
Diffuse Type ◽  
Rna Seq ◽  
Tissue Samples ◽  
Diffuse Type Gastric Cancer ◽  
Tissue Microarray Analysis

Abstract Background Although recent advances in high-throughput technology have provided many insights into gastric cancer (GC), few reliable biomarkers for diffuse-type GC have been identified. Here, we aim to identify a prognostic and predictive signature of diffuse-type GC heterogeneity. Methods We analyzed RNA-seq-based transcriptome data to identify a molecular signature in 150 gastric tissue samples including 107 diffuse-type GCs. The predictive value of the signature was verified using other diffuse-type GC samples in three independent cohorts (n = 466). Log-rank and Cox regression analyses were used to estimate the association between the signature and prognosis. The signature was also characterized by somatic variant analyses and tissue microarray analysis between diffuse-type GC subtypes. Results Transcriptomic profiling of RNA-seq data identified a signature which revealed distinct subtypes of diffuse-type GC: the intestinal-like (INT) and core diffuse-type (COD) subtypes. The signature showed high predictability and independent clinical utility in diffuse-type GC prognosis in other patient cohorts (HR 2.058, 95% CI 1.53–2.77, P = 1.76 × 10–6). Integrative mutational and gene expression analyses demonstrated that the COD subtype was responsive to chemotherapy, whereas the INT subtype was responsive to immunotherapy with an immune checkpoint inhibitor (ICI). Tissue microarray analysis showed the practical utility of IGF1 and NXPE2 for predicting diffuse-type GC heterogeneity. Conclusions We present a molecular signature that can identify diffuse-type GC patients who display different clinical behaviors as well as responses to chemotherapy or ICI treatment.

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