Deciphering the underlying genetic and epigenetic events leading to gastric carcinogenesis

Vogiatzi, Paraskevi; Vindigni, Carla; Roviello, Franco; Renieri, Alessandra; Giordano, Antonio

doi:10.1002/jcp.20982

Cited by 91 publications

(76 citation statements)

References 107 publications

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“…Several environmental factors, including Helicobacter pylori infection, consumption of salted and nitrated foods, and cigarette smoking, have been found to be associated with the risk of developing GC [6][7][8][9]. In addition to environmental factors, genetic factors also play an important role in GC etiology, and previous reports suggest that combinations of genetic and/or epigenetic changes in oncogenic and tumor suppressor pathways may drive GC [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Prognostic impact of expression and methylation status of DENN/MADD domain-containing protein 2D in gastric cancer

et al. 2014

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Background Patients with advanced gastric cancer (GC) have an adverse prognosis even after curative resection. Development of novel diagnostic and therapeutic approaches for GC is urgently required. Methods The expression and methylation status of DENN/MADD domain-containing protein 2D (DEN-ND2D), a member of the membrane trafficking proteins, were evaluated in 12 GC cell lines and 112 pairs of surgical specimens. Subgroup analysis based on tumor differentiation, location, and morphology was also performed. Expression and distribution of DENND2D protein were determined by immunohistochemistry. Results The majority of GC cell lines (75 %) and tissues (79 %) showed reduced expression of DENND2D mRNA compared with noncancerous gastric tissues. GC tissues showed a significantly lower mean expression level of mRNA and a higher frequency of promoter hypermethylation of DENND2D than corresponding noncancerous tissues. No significant differences in DENND2D mRNA expression and methylation status were found between GC subtypes categorized by tumor differentiation, location, and morphology. The expression patterns of DENND2D protein were confirmed to be consistent with those of DENND2D mRNA. Downregulation of DENND2D mRNA in GC tissues was significantly associated with factors related to more advanced GC and subsequent adverse prognosis. Among 72 patients who underwent R0 resection, downregulation of DENND2D mRNA in GC tissues was an independent prognostic factor and associated with early recurrence. Conclusions Our results suggested that DENND2D is a putative tumor suppressor gene regulated by promoter hypermethylation in GC. Downregulation of DENND2D can serve as a novel tumor biomarker to predict progression and early recurrence of all types of GC.

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Section: Introductionmentioning

confidence: 99%

Prognostic impact of expression and methylation status of DENN/MADD domain-containing protein 2D in gastric cancer

et al. 2014

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“…Moreover, promoter hypermethylation of tumour-related genes has also been proposed as a novel biomarker for detecting cancer and predicting prognosis (Jones and Baylin, 2007). We and others have shown earlier that many tumour-related genes were frequently silenced through promoter hypermethylation in gastric carcinoma as well as pre-malignant gastric lesions (Leung et al, 2001; Lee et al, 2002;To et al, 2002;Chan et al, 2004;Choi and Wu, 2005;Chan and Rashid, 2006;Sato and Meltzer, 2006;Cheng et al, 2007;Ushijima, 2007;Vogiatzi et al, 2007), suggesting that promoter hypermethylation can be utilised as biomarkers for early detection of gastric cancer.…”

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confidence: 99%

Fibulin 1 is downregulated through promoter hypermethylation in gastric cancer

et al. 2008

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Tumour suppressor genes (TSGs) were frequently inactivated through promoter hypermethylation in gastric carcinoma as well as pre-malignant gastric lesions, suggesting that promoter hypermethylation can be used as a marker to define novel TSGs and also biomarkers for early detection of gastric cancer. In an effort to search for such genes aberrantly methylated in gastric cancer development, fibulin 1 (FBLN1) was found as a candidate TSG epigenetically downregulated in gastric cancer. FBLN1 expression was downregulated in all of gastric cancer cell lines used (100%, 7 out of 7) and the primary gastric carcinoma tissues (84%, 86 out of 102) and significantly restored after pharmacological demethylation. Hypermethylation of the FBLN1 promoter was frequently (71%, 5 out of 7) detected in gastric cancer cell lines and primary gastric carcinoma tissues. Ectopic expression of FBLN1 led to the growth inhibition of gastric cancer cells through the induction of apoptosis. In summary, FBLN1 was identified as a novel candidate TSG epigenetically downregulated in gastric cancer.

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“…Although with variations in prevalence, these studies revealed somatic mutations in both genes that might be relevant in gastric carcinogenesis [50][51][52][53][54][55] . In addition to multiple genetic alterations, the initiation and progression of gastric cancer are also associated to epigenetic changes [56,57] . Histone modification and promoter CpG methylation alter cancer-related gene expression and are frequently involved in carcinogenesis [58] .…”

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confidence: 99%

Role of the Wnt/β-catenin pathway in gastric cancer: An in-depth literature review

Chiurillo

2015

WJEM

270

219

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Gastric cancer remains one of the most common cancers worldwide and one of the leading cause for cancerrelated deaths. Gastric adenocarcinoma is a multifactorial disease that is genetically, cytologically and architecturally more heterogeneous than other gastrointestinal carcinomas. The identification of specific membrane, intracellular, and extracellular components of the Wnt pathway has revealed potential targets for gastric cancer therapy. High-throughput "omics" approaches will help in the search for Wnt pathway antagonist in the near future.

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Deciphering the underlying genetic and epigenetic events leading to gastric carcinogenesis

Cited by 91 publications

References 107 publications

Prognostic impact of expression and methylation status of DENN/MADD domain-containing protein 2D in gastric cancer

Prognostic impact of expression and methylation status of DENN/MADD domain-containing protein 2D in gastric cancer

Fibulin 1 is downregulated through promoter hypermethylation in gastric cancer

Role of the Wnt/β-catenin pathway in gastric cancer: An in-depth literature review

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