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Erschienen in: Tumor Biology 2/2014

01.02.2014 | Research Article

Association of COX2 gene hypomethylation with intestinal type gastric cancer in samples of patients from northern Brazil

verfasst von: Cynthia Farias Vieira de Melo, Carolina Oliveira Gigek, Juarez Nóbrega da Silva, Marilia de Arruda Cardoso Smith, Rubistenia Miranda de Araújo, Rommel Rodríguez Burbano, Eleonidas Moura Lima

Erschienen in: Tumor Biology | Ausgabe 2/2014

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Abstract

To verify the methylation status of THBS1, GPX3, and COX2 genes and to evaluate their association with Helicobacter pylori in gastric adenocarcinomas. Methylation-sensitive restriction enzyme PCR assay was performed in 16 diffuse type gastric cancer samples, 23 intestinal type, and 15 normal stomach tissue. The presence of H. pylori was performed by amplification of the fragment of the 16S rRNA. Statistical analyses were performed using Fisher’s exact test. The hypermethylation of GPX3, THBS1, and COX2 occurred in 18 (n = 7), 5 (n = 2), and 36 % (n = 14) of gastric cancer samples, respectively, whereas in normal samples, it was found in 13, 7, and 67 %. The presence of H. pylori was detected in 67 % of gastric cancer samples and 67 % in normal gastric samples. The methylation of THBS1 and GPX3 was not significantly different between the types of tumors, normal sample, the presence of H. pylori, or clinicopathological variables studied (P > 0.05). However, the methylation status of the gene COX2 is significantly different between normal tissue and intestinal type gastric cancer (P = 0.02). Therefore, our results suggest that the methylation status of the gene COX2 is associated with the intestinal type of gastric cancer.
Literatur
1.
Zurück zum Zitat Terry MB, Delgado-Cruzata L, Vin-Raviv N, Wu HC, Santella RM. DNA methylation in white blood cells. Association with risk factors in epidemiologic studies. Epigenetics. 2011;6:828–37.PubMedCrossRef Terry MB, Delgado-Cruzata L, Vin-Raviv N, Wu HC, Santella RM. DNA methylation in white blood cells. Association with risk factors in epidemiologic studies. Epigenetics. 2011;6:828–37.PubMedCrossRef
2.
Zurück zum Zitat Everatt R, Tamosiunas A, Kuzmickiene I, Virviciute D, Radisauska R, Reklaitiene R, et al. Alcohol consumption and risk of gastric cancer: a cohort study of men in Kaunas, Lithuania, with up to 30 years follow-up. BMC Cancer. 2012;12:1–12.CrossRef Everatt R, Tamosiunas A, Kuzmickiene I, Virviciute D, Radisauska R, Reklaitiene R, et al. Alcohol consumption and risk of gastric cancer: a cohort study of men in Kaunas, Lithuania, with up to 30 years follow-up. BMC Cancer. 2012;12:1–12.CrossRef
3.
Zurück zum Zitat Peña S, Sampieri CL, León-Córdoba K. Metaloproteasas de la matriz extracelular como marcadores moleculares en cáncer gástrico. Med Clin. 2010;134:123–6.CrossRef Peña S, Sampieri CL, León-Córdoba K. Metaloproteasas de la matriz extracelular como marcadores moleculares en cáncer gástrico. Med Clin. 2010;134:123–6.CrossRef
4.
Zurück zum Zitat Stewart CJR, Crook ML. CD147 (EMMPRIN) and matrix metalloproteinase-2 expression in uterine endometrioid adenocarcinoma. Pathol Res Pract. 2011;207:30–6.PubMedCrossRef Stewart CJR, Crook ML. CD147 (EMMPRIN) and matrix metalloproteinase-2 expression in uterine endometrioid adenocarcinoma. Pathol Res Pract. 2011;207:30–6.PubMedCrossRef
5.
Zurück zum Zitat Kornfeld JW, Meder S, Wohlberg M, Friedrich RE, Rau T, Riethdorf L, et al. Overexpression of TACE and TIMP3 mRNA in head and neck cancer: association with tumour development and progression. Br J Cancer. 2011;104:138–45.PubMedCentralPubMedCrossRef Kornfeld JW, Meder S, Wohlberg M, Friedrich RE, Rau T, Riethdorf L, et al. Overexpression of TACE and TIMP3 mRNA in head and neck cancer: association with tumour development and progression. Br J Cancer. 2011;104:138–45.PubMedCentralPubMedCrossRef
6.
Zurück zum Zitat Gigek CO, Chen ES, Calcagno DQ, Wisnieski F, Burbano RR, Smith MAC. Epigenetic mechanisms in gastric cancer. Epigenomics. 2012;4:279–94.PubMedCrossRef Gigek CO, Chen ES, Calcagno DQ, Wisnieski F, Burbano RR, Smith MAC. Epigenetic mechanisms in gastric cancer. Epigenomics. 2012;4:279–94.PubMedCrossRef
7.
Zurück zum Zitat Kang SH, Choi HH, Kim SG, Jong HS, Kim NK, Kim SJ, et al. Transcriptonal inactivation of the tissue inhibitor of metalloproteinase-3 gene by DNA hypermethylation of the 59-CpG island in human gastric cancer cell lines. Int J Cancer. 2000;86:632–5.PubMedCrossRef Kang SH, Choi HH, Kim SG, Jong HS, Kim NK, Kim SJ, et al. Transcriptonal inactivation of the tissue inhibitor of metalloproteinase-3 gene by DNA hypermethylation of the 59-CpG island in human gastric cancer cell lines. Int J Cancer. 2000;86:632–5.PubMedCrossRef
8.
Zurück zum Zitat Kang GH, Shim YH, Jung HY, Kim WH, Ro JY, Rhyu MG. CpG island methylation in premalignant stages of gastric carcinoma. Cancer Res. 2001;61:2847–51.PubMed Kang GH, Shim YH, Jung HY, Kim WH, Ro JY, Rhyu MG. CpG island methylation in premalignant stages of gastric carcinoma. Cancer Res. 2001;61:2847–51.PubMed
9.
Zurück zum Zitat Kanyama Y, Hibi K, Nakayama H, Kodera Y, Ito K, Akiyama S, et al. Detection of p16 promoter hypermethylation in serum of gastric cancer patients. Cancer Sci. 2003;94:418–20.PubMedCrossRef Kanyama Y, Hibi K, Nakayama H, Kodera Y, Ito K, Akiyama S, et al. Detection of p16 promoter hypermethylation in serum of gastric cancer patients. Cancer Sci. 2003;94:418–20.PubMedCrossRef
10.
Zurück zum Zitat Guimarães AC, Lima EM, Khayat AS, Girão Faria MH, Barem Rabenhorst SH, Pitombeira MV, et al. Interrelationships among chromosome aneuploidy, promoter hypermethylation, and protein expression of the CDKN2A gene in individuals from northern Brazil with gastric adenocarcinoma. Cancer Genet Cytogenet. 2007;179:45–51.PubMedCrossRef Guimarães AC, Lima EM, Khayat AS, Girão Faria MH, Barem Rabenhorst SH, Pitombeira MV, et al. Interrelationships among chromosome aneuploidy, promoter hypermethylation, and protein expression of the CDKN2A gene in individuals from northern Brazil with gastric adenocarcinoma. Cancer Genet Cytogenet. 2007;179:45–51.PubMedCrossRef
11.
Zurück zum Zitat Lima EM, Leal MF, Burbano RR, Khayat AS, Assumpção PP, Bello MJ, et al. Methylation status of ANAPC1, CDKN2A and TP53 promoter genes in individuals with gastric cancer. Braz J Med Biol Res. 2008;41:539–43.PubMedCrossRef Lima EM, Leal MF, Burbano RR, Khayat AS, Assumpção PP, Bello MJ, et al. Methylation status of ANAPC1, CDKN2A and TP53 promoter genes in individuals with gastric cancer. Braz J Med Biol Res. 2008;41:539–43.PubMedCrossRef
12.
Zurück zum Zitat Falck E, Karlsson S, Carlsson J, Helenius G, Karlsson M, Klinga-Levan K. Loss of glutathione peroxidase 3 expression is correlated with epigenetic mechanisms in endometrial adenocarcinoma. Cancer Cell Int. 2010;10:1–9.CrossRef Falck E, Karlsson S, Carlsson J, Helenius G, Karlsson M, Klinga-Levan K. Loss of glutathione peroxidase 3 expression is correlated with epigenetic mechanisms in endometrial adenocarcinoma. Cancer Cell Int. 2010;10:1–9.CrossRef
13.
Zurück zum Zitat Gigek CO, Lisboa LC, Leal MF, Silva PN, Lima EM, Khayat AS, et al. SMARCA5 methylation and expression in gastric cancer. Cancer Invest. 2011;29:162–6.PubMedCrossRef Gigek CO, Lisboa LC, Leal MF, Silva PN, Lima EM, Khayat AS, et al. SMARCA5 methylation and expression in gastric cancer. Cancer Invest. 2011;29:162–6.PubMedCrossRef
14.
Zurück zum Zitat Saslow DLW, Zabrenetzky VS, Vanhoutte K, Frazier WA, Roberts DD, Steeg PS. Transfection of thrombospondin 1 complementary DNA into a human breast carcinoma cell line reduces primary tumor growth, metastatic potential, and angiogenesis. Cancer Res. 1994;24:6504–11. Saslow DLW, Zabrenetzky VS, Vanhoutte K, Frazier WA, Roberts DD, Steeg PS. Transfection of thrombospondin 1 complementary DNA into a human breast carcinoma cell line reduces primary tumor growth, metastatic potential, and angiogenesis. Cancer Res. 1994;24:6504–11.
15.
Zurück zum Zitat Oue N, Matsumura S, Nakayama H, Kitadai Y, Taniyama K, Matsusaki K, et al. Reduced expression of the TSP1 gene and its association with promoter hypermethylation in gastric carcinoma. Oncology. 2003;64:423–9.PubMedCrossRef Oue N, Matsumura S, Nakayama H, Kitadai Y, Taniyama K, Matsusaki K, et al. Reduced expression of the TSP1 gene and its association with promoter hypermethylation in gastric carcinoma. Oncology. 2003;64:423–9.PubMedCrossRef
16.
Zurück zum Zitat Guo W, Dong Z, He M, Guo Y, Guo J, Chen Z, et al. Aberrant methylation of thrombospondin-1 and its association with reduced expression in gastric cardia adenocarcinoma. J Biomed Biotechnol. 2010;2010:1–10. Guo W, Dong Z, He M, Guo Y, Guo J, Chen Z, et al. Aberrant methylation of thrombospondin-1 and its association with reduced expression in gastric cardia adenocarcinoma. J Biomed Biotechnol. 2010;2010:1–10.
17.
Zurück zum Zitat Takahashi K, Akasaka M, Yamamoto Y, Kobayashi C, Mizoguchi J, Koyama J. Primary structure of human plasma glutathione peroxidase deduced from cDNA sequences. J Biochem. 1990;108:145–8.PubMed Takahashi K, Akasaka M, Yamamoto Y, Kobayashi C, Mizoguchi J, Koyama J. Primary structure of human plasma glutathione peroxidase deduced from cDNA sequences. J Biochem. 1990;108:145–8.PubMed
18.
Zurück zum Zitat Wang D, Dubois RN. Therapeutic potential of peroxisome proliferator-activated receptors in chronic inflammation and colorectal cancer. Gastroenterol Clin North Am. 2010;39:697–707.PubMedCentralPubMedCrossRef Wang D, Dubois RN. Therapeutic potential of peroxisome proliferator-activated receptors in chronic inflammation and colorectal cancer. Gastroenterol Clin North Am. 2010;39:697–707.PubMedCentralPubMedCrossRef
19.
Zurück zum Zitat Chen B, Rao X, House MG, Nephew KP, Cullen KJ, Guo Z. GPx3 promoter hypermethylation is a frequent event in human cancer and is associated with tumorigenesis and chemotherapy response. Cancer Lett. 2011;309:37–45.PubMedCrossRef Chen B, Rao X, House MG, Nephew KP, Cullen KJ, Guo Z. GPx3 promoter hypermethylation is a frequent event in human cancer and is associated with tumorigenesis and chemotherapy response. Cancer Lett. 2011;309:37–45.PubMedCrossRef
20.
Zurück zum Zitat Majack RA, Cook SC, Bornstein P. Platelet-derived growth factor and heparin-like glycosaminoglycans regulate thrombospondin synthesis and deposition in the matrix by smooth muscle cells. J Cell Biol. 1985;101:1059–70.PubMedCrossRef Majack RA, Cook SC, Bornstein P. Platelet-derived growth factor and heparin-like glycosaminoglycans regulate thrombospondin synthesis and deposition in the matrix by smooth muscle cells. J Cell Biol. 1985;101:1059–70.PubMedCrossRef
22.
Zurück zum Zitat Fleitas T, Martínez-Sales V, Vila V, Reganon E, Mesado D, Martín M, et al. VEGF and TSP1 levels correlate with prognosis in advanced non-small cell lung cancer. Clin Transl Oncol. 2013. doi:10.1007/s12094-013-1020-6.PubMed Fleitas T, Martínez-Sales V, Vila V, Reganon E, Mesado D, Martín M, et al. VEGF and TSP1 levels correlate with prognosis in advanced non-small cell lung cancer. Clin Transl Oncol. 2013. doi:10.​1007/​s12094-013-1020-6.PubMed
23.
Zurück zum Zitat Hur H, Lee SR, Xuan Y, Kim YB, Lim YA, Cho YK, et al. The effects of Helicobacter pylori on the prognosis of patients with curatively resected gastric cancers in a population with high infection rate. J Korean Surg Soc. 2012;83:203–11.PubMedCentralPubMedCrossRef Hur H, Lee SR, Xuan Y, Kim YB, Lim YA, Cho YK, et al. The effects of Helicobacter pylori on the prognosis of patients with curatively resected gastric cancers in a population with high infection rate. J Korean Surg Soc. 2012;83:203–11.PubMedCentralPubMedCrossRef
24.
Zurück zum Zitat Bhandari A, Crowe SE. Helicobacter pylori in gastric malignancies. Curr Gastroenterol Rep. 2012;14:489–96.PubMedCrossRef Bhandari A, Crowe SE. Helicobacter pylori in gastric malignancies. Curr Gastroenterol Rep. 2012;14:489–96.PubMedCrossRef
25.
Zurück zum Zitat Jee CD, Kim MA, Jung EJ, Kim J, Kim WH. Identification of genes epigenetically silenced by CpG methylation in human gastric carcinoma. Eur J Cancer. 2009;45:1282–93.PubMedCrossRef Jee CD, Kim MA, Jung EJ, Kim J, Kim WH. Identification of genes epigenetically silenced by CpG methylation in human gastric carcinoma. Eur J Cancer. 2009;45:1282–93.PubMedCrossRef
26.
Zurück zum Zitat Mrena J, Alexandra T, Ari R. Cyclooxygenase-2 and gastric cancer. Cancer Metastasis Rev. 2011;30:387–95.PubMedCrossRef Mrena J, Alexandra T, Ari R. Cyclooxygenase-2 and gastric cancer. Cancer Metastasis Rev. 2011;30:387–95.PubMedCrossRef
27.
Zurück zum Zitat Chang YJ, Wu MS, Lin JT, Sheu BS, Muta T, Inoue H, et al. Induction of cyclooxygenase-2 overexpression in human gastric epithelial cells by Helicobacter pylori involves TLR2/TLR9 and c-Src-dependent nuclear factor kappaB activation. Mol Pharmacol. 2004;66:1465–77.PubMedCrossRef Chang YJ, Wu MS, Lin JT, Sheu BS, Muta T, Inoue H, et al. Induction of cyclooxygenase-2 overexpression in human gastric epithelial cells by Helicobacter pylori involves TLR2/TLR9 and c-Src-dependent nuclear factor kappaB activation. Mol Pharmacol. 2004;66:1465–77.PubMedCrossRef
28.
Zurück zum Zitat Rodenhise DI. Epigenetic contributions to cancer metastasis. Clin Exp Metastasis. 2009;26:5–18.CrossRef Rodenhise DI. Epigenetic contributions to cancer metastasis. Clin Exp Metastasis. 2009;26:5–18.CrossRef
29.
Zurück zum Zitat Wang B, Guo CQ, Sun C, Sun QL, Liu GY, Li DG. Mechanism and clinical significance of cyclooxygenase-2 expression in gastric cancer. World J Gastroenterol. 2005;11:3240–4.PubMed Wang B, Guo CQ, Sun C, Sun QL, Liu GY, Li DG. Mechanism and clinical significance of cyclooxygenase-2 expression in gastric cancer. World J Gastroenterol. 2005;11:3240–4.PubMed
30.
Zurück zum Zitat Shi H, Xu JM, Hu NZ, Xie HJ. Prognostic significance of expression o cyclooxygenase-2 and vascular endothelial growth factor in human gastric carcinoma. World J Gastroenterol. 2003;9:1421–6.PubMed Shi H, Xu JM, Hu NZ, Xie HJ. Prognostic significance of expression o cyclooxygenase-2 and vascular endothelial growth factor in human gastric carcinoma. World J Gastroenterol. 2003;9:1421–6.PubMed
31.
Zurück zum Zitat Xue YW, Zhang QF, Zhu ZB, Wang Q, Fu SB. Expression of cyclooxygenase-2 and clinicopathologic features in human gastric denocarcinoma. World J Gastroenterol. 2003;9:250–3.PubMed Xue YW, Zhang QF, Zhu ZB, Wang Q, Fu SB. Expression of cyclooxygenase-2 and clinicopathologic features in human gastric denocarcinoma. World J Gastroenterol. 2003;9:250–3.PubMed
Metadaten
Titel
Association of COX2 gene hypomethylation with intestinal type gastric cancer in samples of patients from northern Brazil
verfasst von
Cynthia Farias Vieira de Melo
Carolina Oliveira Gigek
Juarez Nóbrega da Silva
Marilia de Arruda Cardoso Smith
Rubistenia Miranda de Araújo
Rommel Rodríguez Burbano
Eleonidas Moura Lima
Publikationsdatum
01.02.2014
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 2/2014
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1148-6

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