p16 promoter hypermethylation: A useful serum marker for early detection of gastric cancer

Abbaszadegan, Mohammad Reza; Moaven, Omeed; Sima, Hamid Reza; Kamran, Ghafarzadegan; Arabi, Azadeh; Forghani, Maryam; Raziee, Hamid; Mashhadinejad, Ali; Jafarzadeh, Mostafa; Shandiz, Ehsan Esmaili; Dadkhah, Ezzat

doi:10.3748/wjg.14.2055

Cited by 79 publications

(48 citation statements)

References 26 publications

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“…Increased methylation is associated with inflammation, dysplasia, and malignant transformation, suggesting the involvement of epigenetic changes in inflammation-associated carcinogenesis (18,19). In gastric cancer, several tumor suppressor genes, such as p16 INK4 , E-cadherin, and RUNX3, are hypermethylated in their promoter (20)(21)(22). DNA methylation in mammalian cells is catalyzed by enzymes of the DNA methyltransferase (DNMT) family, including DNMT1, DNMT3A, DNMT3B, and DNMT3L (23).…”

Section: Introductionmentioning

confidence: 99%

Tumor-Associated Macrophages Promote Epigenetic Silencing of Gelsolin through DNA Methyltransferase 1 in Gastric Cancer Cells

Wang

Chen

Yang

et al. 2017

Cancer Immunology Research

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Epigenetic repression of the tumor suppressor gelsolin (GSN) is frequently observed in cancers. Chronic inflammation can promote tumor progression via aberrant DNA methylation. In this study, we investigated the role of tumor-associated macrophages (TAMs) in DNA methylation of the GSN gene during gastric cancer progression. Immunofluorescence staining of 121 gastric cancer tissues showed aberrant localization of GSN and DNA methyltransferase 1 (DNMT1) and juxtaposition of DNMT1 and M2 TAMs. Decreased GSN protein and mRNA expression and increased DNA methylation in the GSN promoter were observed in gastric cancer cell lines and clinical specimens. To examine the effect of TAMs on DNA methylation in gastric cancer cells, we performed in vitro coculture assays and found increased DNMT1 expression but decreased GSN expression in gastric cancer cells after coculture with U937 cells. Knockdown of DNMT1 expression in gastric cancer cells could abort U937 coculture-mediated GSN downregulation. Meanwhile, CCL5 was the main chemokine upregulated in coculture medium. Treatment with CCL5 could induce DNMT1 expression in gastric cancer cells via STAT3 signaling. Inhibiting DNMT1 activity with procainamide, inhibiting DNA methylation with 5-AZA, or inhibiting CCL5/CCR5 signaling with maraviroc reduced tumor growth in vivo. In conclusion, upregulation of DNMT1 by CCL5/CCR5/STAT3 signaling is critical for TAM-mediated GSN silencing in gastric cancer. This study identified potential targets for gastric cancer therapy. Cancer Immunol Res; 5(10); 885-97. Ó2017 AACR.

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Section: Introductionmentioning

confidence: 99%

Tumor-Associated Macrophages Promote Epigenetic Silencing of Gelsolin through DNA Methyltransferase 1 in Gastric Cancer Cells

Wang

Chen

Yang

et al. 2017

Cancer Immunology Research

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“…According to Lauren's histological classification, it is subdivided into diffuse and intestinal pathologic subtypes, each having different epidemiological and prognostic features [5,6] . Multiple genetic and epigenetic alterations in oncogenes, tumor-suppressor genes, cellcycle regulators, cell adhesion molecules and DNA repair genes are implicated in the multistep process of human stomach carcinogenesis [6,7] , and different genetic pathways have been proposed for these two subtypes of gastric carcinoma [2] . Depth of invasion and lymph node metastasis result from the polygene, and their protein expression in gastric carcinoma.…”

Section: Introductionmentioning

confidence: 99%

“…This polymorphic integ ral membrane glycoprotein, which is expressed by many cell types, serves as the principal transmembrane hyaluronate receptor. It is considered a determinant of metastatic and invasive behavior in different malignancies, such as lung carcinoma, malignant melanoma, leukemia, breast cancer, as well as gastrointestinal carcinomas [2,9,10] . On the other hand, contradictory reports concerning the biological role of CD44 in tumorigenesis and its clinical value in prognosis have also been presented [9] .…”

Section: Introductionmentioning

confidence: 99%

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Expression of cell adhesion molecule CD44 in gastric adenocarcinoma and its prognostic importance

Ghaffarzadehgan¹,

Jafarzadeh²,

Raziee³

et al. 2008

WJG

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used for histological evaluation, including the type (Lauren's classification) and grading of the tumor. The expression of CD44 in the gastric adenocarcinoma mucosa and the adjacent mucosa were determined by immunohistochemistry. The survival analysis was obtained using the Kaplan-Meier test. RESULTS: Of 100 patients, 74 (74%) patients were male. The tumors were categorized as intestinal type (78%) or diffuse type (22%). Sixty-five percent of patients were CD44-positive. CD44 expression was not detected in normal gastric mucosa. Rather, CD44 was more commonly expressed in the intestinal subtype (P = 0.002). A significant relation was seen between the grade of tumor and the expression of CD44 (P = 0.014). The survival analysis showed a poor prognosis of patients with CD44-positive tumors (P = 0.008); and this was more prominent in the intestinal (P = 0.001) rather than diffuse type. CONCLUSION: Cell adhesion molecule CD44 is highly expressed in gastric adenocarcinoma. CD44 expression is correlated with a poor prognosis in patients with the intestinal type of gastric adenocarcinoma. CD44 can, therefore, be utilized as a prognostic marker for this group of patients. Abstract AIM: To evaluate the relation of cluster of differentiation 44 (CD44) expression with clinicopathological features of gastric adenocarcinoma, and also its effect on prognosis with an emphasis on the differences between intestinal and diffuse types. METHODS: From 2000 to 2006, 100 patients with gastric adenocarcinoma, who had undergone total or subtotal gastrectomy without any prior treatment, were studied. Haematoxylin & eosin (HE) staining was

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“…Serving as the main transmembrane hyaluronate receptor, CD44 is regarded not only as a cell adhesion molecule, but also as a determinant of metastatic and invasive behavior in a variety of malignancies, including malignant melanoma, lung carcinoma, breast cancer, leukemia and gastrointestinal carcinomas (39)(40)(41)(42).…”

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confidence: 99%

Low-dose interleukin-8 induces the adhesion, migration and invasion of the gastric cancer SGC-7901 cell line

Shi

Wei

2015

Oncology Letters

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Abstract. , an important inflammatory cytokine, is strongly associated with gastric cancer development and metastasis. High-dose (>1 ng/ml) IL-8 has been revealed to promote the adhesion, migration and invasion of human gastric cancer SGC-7901 cells in a dose-dependent manner. However, the IL-8 level produced by gastric cells is marginal, at even less than 1 ng/ml. It is unclear whether low-dose IL-8 also induces these capacities. In the present study, the effect of low-dose IL-8 on the adhesion, migration and invasion of the SGC-7901 cell line and the underlying molecular mechanism with regard to cluster of differentiation 44 (CD44) were investigated. The SGC-7901 cells were exposed to various concentrations of IL-8 (0, 0.2, 0.5, 0.8 and 1 ng/ml) in vitro. The adhesion of the SGC-7901 cells to fibronectin, an extracellular matrix component, was then detected by cell counting kit 8 assay. Migration and invasion abilities were evaluated by wound scratch and Transwell chamber assays. In addition, protein and mRNA levels of CD44 were measured using immunofluorescence and western blotting, and quantitative polymerase chain reaction, respectively, in cells cultured for 72 h. Following the exposure of the SGC-7901 cells to the various low doses of IL-8, the cell adhesion, migration and invasion capacities were promoted by IL-8, but not in a significant dose-dependent manner. Low-dose IL-8 upregulated the protein and mRNA expression of CD44. In conclusion, low-dose IL-8 potently induces the adhesion, migration and invasion of SGC-7901 cells, and the regulation of CD44 expression is one of the potential molecular mechanisms involved.

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p16 promoter hypermethylation: A useful serum marker for early detection of gastric cancer

Abstract: p16 promoter hypermethylation is an important event in gastric carcinogenesis. It is the principle mechanism of p16 gene silencing. It is related to malignant tumor behavior. Detection of DNA methylation in serum may be a biomarker for early detection of gastric cancer.

Cited by 79 publications

References 26 publications

Tumor-Associated Macrophages Promote Epigenetic Silencing of Gelsolin through DNA Methyltransferase 1 in Gastric Cancer Cells

Tumor-Associated Macrophages Promote Epigenetic Silencing of Gelsolin through DNA Methyltransferase 1 in Gastric Cancer Cells

Expression of cell adhesion molecule CD44 in gastric adenocarcinoma and its prognostic importance

Low-dose interleukin-8 induces the adhesion, migration and invasion of the gastric cancer SGC-7901 cell line

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