Molecular-pathological prognostic factors of gastric cancer: a review

Yasui, Wataru; Oue, Naohide; Aung, Phyu P.; Matsumura, Shunji; Shutoh, Mariko; Nakayama, Hirofumi

doi:10.1007/s10120-005-0320-0

Cited by 241 publications

(182 citation statements)

References 54 publications

(53 reference statements)

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“…These data are in accordance with the pathophysiological concept of an association between a disturbed intercellular adhesion and a poor prognosis in gastric cancer (Yasui et al, 2005). Particularly, the loss of E-cadherin has been linked to an unfavourable clinical outcome in gastric cancer patients (Yonemura et al, 1995(Yonemura et al, , 2000Guilford, 1999).…”

Section: Discussionsupporting

confidence: 82%

Loss of the coxsackie and adenovirus receptor contributes to gastric cancer progression

et al. 2009

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Loss of the coxsackie and adenovirus receptor (CAR) has previously been observed in gastric cancer. The role of CAR in gastric cancer pathobiology, however, is unclear. We therefore analysed CAR in 196 R 0 -resected gastric adenocarcinomas and noncancerous gastric mucosa samples using immunohistochemistry and immunofluorescence. Coxsackie and adenovirus receptor was found at the surface and foveolar epithelium of all non-neoplastic gastric mucosa samples (n ¼ 175), whereas only 56% of gastric cancer specimens showed CAR positivity (Po0.0001). Loss of CAR correlated significantly with decreased differentiation, increased infiltrative depths, presence of distant metastases, and was also associated with reduced carcinoma-specific survival. To clarify whether CAR impacts the tumorbiologic properties of gastric cancer, we subsequently determined the role of CAR in proliferation, migration, and invasion of gastric cancer cell lines by application of specific CAR siRNA or ectopic expression of a human full-length CAR cDNA. These experiments showed that RNAi-mediated CAR knock down resulted in increased proliferation, migration, and invasion of gastric cancer cell lines, whereas enforced ectopic CAR expression led to opposite effects. We conclude that the association of reduced presence of CAR in more severe disease states, together with our findings in gastric cancer cell lines, suggests that CAR functionally contributes to gastric cancer pathogenesis, showing features of a tumour suppressor.

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Section: Discussionsupporting

confidence: 82%

Loss of the coxsackie and adenovirus receptor contributes to gastric cancer progression

et al. 2009

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“…the relatively asymptomatic nature in the early stage of the disease and the lack of adequate screening methods have resulted in the majority of GC patients diagnosed at an advanced stage of the disease. the prognosis of patients with advanced cancer still remains poor due to its high recurrence rate and metastatic features including lymph node invasion, peritoneal implantation and liver metastasis (3)(4)(5). therefore, the most effective way to improve patient prognosis is the prediction of GC carcinogenesis and metastasis at an early stage.…”

Section: Introductionmentioning

confidence: 99%

Tissue metabolomic fingerprinting reveals metabolic disorders associated with human gastric cancer morbidity

Wang²,

Liu³

et al. 2011

Oncol Rep

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Abstract. the principal way to improve the outcome of gastric cancer (GC) is to predict carcinogenesis and metastasis at an early stage. the aims of the present study were to test the hypothesis that distinct metabolic profiles are reflected in GC tissues and to further explore potential biomarkers for GC diagnosis. Gas chromatography/mass spectrometry (GC/Ms) was utilized to analyze tissue metabolites from 30 GC patients. A diagnostic model for GC was constructed using orthogonal partial least squares discriminant analysis (OpLs-DA), and the metabolomic data were analyzed using the non-parametric Wilcoxon rank sum test to identify the metabolic tissue biomarkers for GC. Over 100 signals were routinely detected in one single total ion current (tIC) chromatogram, and the OPLS-DA model generated from the metabolic profile of the tissues adequately discriminated the GC tissues from the normal mucosae. Among the low-molecular-weight endogenous metabolites, a total of 41 compounds, such as amino acids, organic acids, carbohydrates, fatty acids and steroids, were detected, and 15 differential metabolites were identified with significant difference (p<0.05). A total of 20 variables were noted which contributed to a great extent in the discriminating OpLs-DA model (VIp value >1.0), among which 12 metabolites were identified using both VIP values (VIP >1) and the Wilcoxon test (p<0.05). In conclusion, the identification of the metabolites associated with GC morbidity potentially revealed perturbations of glycolysis, fatty acid β-oxidation, cholesterol and amino acid metabolism. these results suggest that tissue metabolic profiles have great potential in detecting GC and may aid in understanding its underlying mechanisms.

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“…Overexpression of MMP-1 (Murray et al, 1996), MMP-2 (Papadopoulou et al, 2001), and MMP-3 (Roeb et al, 2004) has been linked to poor prognosis, high tumour stage, and enhanced tumour invasiveness in patients with CRC. These subjective and semiquantitative studies have inspired subsequent investigators to assess genetic polymorphisms in the promoter regions of MMP genes, as this type of DNA sequence alteration can affect cancer susceptibility and malignant phenotype (Yasui et al, 2005).…”

mentioning

confidence: 99%

The collagenase-1 (MMP-1) gene promoter polymorphism - 1607/2G is associated with favourable prognosis in patients with colorectal cancer

et al. 2007

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Matrix metalloproteinase (MMP) overexpression has been implicated in the pathogenesis of colorectal carcinoma (CRC). Accumulating evidence suggests that MMP promoter single nucleotide polymorphisms (SNPs) effecting gene transcription are associated with enhanced susceptibility for the development of malignant disease, increased tumour invasiveness and poor patient survival. The aim of the current investigation was to determine whether such associations exist in a large CRC patient/control study population. Using an allelic discrimination real-time polymerase chain reaction, polymorphisms in the MMP-1, MMP-2 and MMP-3 gene promoters (À1607, À1306, and À1612 bp, respectively) were assessed in normal blood mononuclear cells from patients with CRC (n ¼ 503) and control subjects (n ¼ 471). Genotypes corresponding to each MMP SNP were correlated with tumour characteristics and clinical outcome. The frequency of each genotype was not statistically different between patients and control subjects and no significant differences were noted between the genotypes and tumour characteristics for the three MMP SNPs. CRC patients with the 2G/2G genotype for the MMP-1 SNP had significantly better 5-year survival compared to patients with a 1G allele (Po0.05). Our results demonstrate that CRC patients with a 2G/2G genotype in the MMP-1 gene promoter SNP have a favourable prognosis. Although our results were unexpected, given that this genotype is associated with enhanced MMP-1 transcriptional activity, they are consistent with recent data highlighting the anti-tumorigenic properties of MMPs.

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Molecular-pathological prognostic factors of gastric cancer: a review

Cited by 241 publications

References 54 publications

Loss of the coxsackie and adenovirus receptor contributes to gastric cancer progression

Loss of the coxsackie and adenovirus receptor contributes to gastric cancer progression

Tissue metabolomic fingerprinting reveals metabolic disorders associated with human gastric cancer morbidity

The collagenase-1 (MMP-1) gene promoter polymorphism - 1607/2G is associated with favourable prognosis in patients with colorectal cancer

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