Molecular biology of gastric carcinoma: From laboratory to bedside

Chan, Annie On‐On; Luk, John M.; Hui, W. M.; Lam, Shiu‐Kum

doi:10.1046/j.1440-1746.1999.02000.x

Cited by 55 publications

(56 citation statements)

References 95 publications

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“…The pathogenesis and molecular alterations leading to these two types of GC are generally considered to differ. [35][36][37] The difference in CpG island hypermethylation between intestinal and diffuse types has not been well characterized. Using different DNA methylation markers and different methodology, CpG island methylator phenotype was found to be associated with 'diffuse' histology in some reports 33,38 but not in others.…”

Section: Methylation In Gc Was Revealed For the First Time In Thismentioning

confidence: 99%

DNA methylation profiles of gastric carcinoma characterized by quantitative DNA methylation analysis

Kang

Lee

Cho

et al. 2008

Laboratory Investigation

154

107

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Transcriptional silencing by CpG island hypermethylation is a potential mechanism for the inactivation of tumor-related genes. Virtually, all types of human cancers show CpG island hypermethylation, and gastric carcinoma (GC) is one of the tumors with a high frequency of aberrant CpG island hypermethylation. In this study, we prescreened DNA methylation of 170 CpG island loci in a training set of 8 paired GC and GC-associated non-neoplastic mucosae (GCN) using MethyLight technology and selected 27 DNA methylation markers showing higher methylation frequency or level in GC than in GCN. These markers were then analyzed in a tester set of 25 paired GC and GCN and 27 chronic gastritis (CG) from non-cancer patients to generate their DNA methylation profiles. We identified 17 novel methylation markers in GC, including SFRP4, SEZ6L, TWIST1, BCL2, KL, TERT, SCGB3A1, IGF2, GRIN2B, SFRP5, DLEC1, HOXA1, CYP1B1, SMAD9, MT1G, NR3C1, and HOXA10. Of the 27 selected CpG island loci, 23 were methylated in GC, GCN, and CG and the remainder four loci (DLEC1, CHFR, CYP1B1, and NR3C1) were only methylated in GC. We found that the number of methylated loci was significantly higher in GC than in GCN or CG and that Helicobacter pylori infection was strongly associated with aberrant CpG island hypermethylation in CG. Hypermethylation was more prevalent in Epstein-Barr virus (EBV)-positive GC than in EBV-negative GC and in diffuse-type GC than in intestinal-type GC. Through our large-scale screening of 170 CpG island loci, we found 17 new DNA methylation markers of GC, which may serve as useful markers that may identify a distinct subset of GC.

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Section: Methylation In Gc Was Revealed For the First Time In Thismentioning

confidence: 99%

DNA methylation profiles of gastric carcinoma characterized by quantitative DNA methylation analysis

Kang

Lee

Cho

et al. 2008

Laboratory Investigation

154

107

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“…Development of gastric cancer is associated with a number of molecular abnormalities, the majority of which affect the downstream signal transduction pathways involved in cell growth and differentiation (2,3). Investigation into such molecules is expected to provide useful prognostic biomarkers of gastric cancer that will aid in determining the treatment plan for individual patients.…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of KLF4 expression in gastric cancer

et al. 2016

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Abstract.To understand the roles of pluripotent stem cell-inducing genes in gastric cancer, the expression of Krüppel-like factor 4 (KLF4), Nanog, octamer-binding transcription factor 4 (Oct4), avian myelocytomatosis viral oncogene homolog (c-Myc) and sex-determining region Y-box 2 (SOX2) was examined using the newly developed gastric carcinoma tissue microarray. The associations between the immunohistochemical expression levels of the pluripotency-inducing factors and the clinicopathological data of 108 patients with gastric cancer were analyzed. No associations were identified between the expression levels of the five pluripotency-inducing factors and the tumor-node-metastasis (TNM) classification or clinicopathological characteristics of the patients. In addition, multivariate analysis revealed no association of Nanog, Oct4, SOX2 or c-Myc with the prognosis of the gastric cancer patients; however, low expression of KLF4 was determined to be an independent negative prognostic factor (P=0.0331), particularly in patients who underwent R0 resection (TNM stages 2 and 3; P=0.0048). In summary, low KLF4 expression was found to be negatively associated with overall survival, and may therefore be a useful prognostic marker in gastric cancer patients. IntroductionGastric cancer is a malignant tumor with a poor prognosis, and the various treatments available at present, including surgery, chemotherapy and radiotherapy, remain unsatisfactory (1). Development of gastric cancer is associated with a number of molecular abnormalities, the majority of which affect the downstream signal transduction pathways involved in cell growth and differentiation (2,3). Investigation into such molecules is expected to provide useful prognostic biomarkers of gastric cancer that will aid in determining the treatment plan for individual patients. For example, methylation of the XIAP-associated factor 1 promoter (4), and expression of 14-3-3σ (5) and miR-200c (6) have been reported to be important for the prediction of poor prognosis in gastric cancer patients; however, further investigation is required.Induced pluripotent stem (iPS) cells are cells that have acquired pluripotency following the introduction of various factors; octamer-binding transcription factor (Oct)3/4 and sex-determining region Y-box 2 (SOX2) plus Krüppel-like factor 4 (KLF4) and avian myelocytomatosis viral oncogene homolog (c-Myc), or Nanog and LIN28 have been shown to induce pluripotency in various murine and human cells (e.g., fibroblasts) (7,8). These pluripotency-inducing factors have been detected in embryonic stem cells, as well as in normal cells and cancer cells, including gastric cancer (9). Although these factors are necessary in order for stem cells to acquire pluripotency, it has been suggested that they may have oncogenic potential in normal cells (10).Expression of SOX2 has been reported to be important for tumorigenicity and chemoresistance (11). However, the inhibition of gastric cancer cell growth and the induction of apoptosis by SOX2 has also been rep...

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“…Advances in the treatment of this disease are likely to come from a fuller understanding of its biology and behavior. The aggressive nature of human gastric carcinoma is related to mutations of various oncogenes and tumor suppressor genes (3)(4)(5) and abnormalities in several growth factors and their receptors (4,5). These abnormalities affect the downstream signal transduction pathways involved in the control of cell growth and differentiation.…”

Section: Introductionmentioning

confidence: 99%

Association between Expression of Transcription Factor Sp1 and Increased Vascular Endothelial Growth Factor Expression, Advanced Stage, and Poor Survival in Patients with Resected Gastric Cancer

Yao¹,

Wang²,

Wei³

et al. 2004

Clinical Cancer Research

188

152

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The biological and clinical behaviors of cancer are affected by multiple molecular pathways that are under the control of transcription factors. Improved understanding of how transcription factors affect cancer biology may lead to improved ability to predict clinical outcome and discovery of novel therapeutic strategies. We evaluated the relationship between Sp1 and vascular endothelial growth factor (VEGF) expression, as well as their effect on survival in 86 cases of resected human gastric cancer. The degree of VEGF expression correlated highly with Sp1 expression (P < 0.01). Patients with high Sp1 expression were 98 times more likely to have high VEGF expression compared with those with negative Sp1 expression. Clinically, negative or weak Sp1 expression was associated with early stage (IA) in gastric cancer. Strong Sp1 expression was more frequently observed among patients with stage IB-IV disease (P ‫؍‬ 0.035). Similarly, whereas strong Sp1 expression was uncommonly observed among patients with N0 or N1 disease (19 and 16%), N2/N3 gastric cancer was associated with strong Sp1 expression (48%; P ‫؍‬ 0.034). Strong Sp1 expression was also associated with inferior survival. The median survival duration in patients who had a tumor with a negative, weak, and strong Sp1 expression was 44, 38, and 8 months (P ‫؍‬ 0.0075), respectively, whereas patients with strong VEGF expression had a shorter survival duration; the difference was not statistically significant. When Sp1 and VEGF expression, stage, completeness of resection, histology, and patient age were entered in a Cox proportional hazards model, strong Sp1 expression (P ‫؍‬ 0.021) and an advanced disease stage (P < 0.001) were independently prognostic of poor survival. Given the importance of Sp1 in the expression of VEGF, our data suggest that dysregulated Sp1 expression and activation play important roles in VEGF overexpression and, thus, gastric cancer development and progression.

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Molecular biology of gastric carcinoma: From laboratory to bedside

Cited by 55 publications

References 95 publications

DNA methylation profiles of gastric carcinoma characterized by quantitative DNA methylation analysis

DNA methylation profiles of gastric carcinoma characterized by quantitative DNA methylation analysis

Prognostic significance of KLF4 expression in gastric cancer

Association between Expression of Transcription Factor Sp1 and Increased Vascular Endothelial Growth Factor Expression, Advanced Stage, and Poor Survival in Patients with Resected Gastric Cancer

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