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Methylation of the claudin‑3 promoter predicts the prognosis of advanced gastric adenocarcinoma

  • Authors:
    • Zhenzhen Zhang
    • Weixing Yu
    • Shuqin Chen
    • Yupeng Chen
    • Linying Chen
    • Sheng Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, The First Affiliated Hospital of Fujian Medical University, Fujian, Fuzhou 350005, P.R. China, Institute of Translational Medicine, Fujian Medical University, Fujian, Fuzhou 350122, P.R. China, Department of Pathology, Fujian Medical University, Fujian, Fuzhou 350122, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 49-60
    |
    Published online on: May 2, 2018
       https://doi.org/10.3892/or.2018.6411
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Abstract

Claudin‑3 expression is associated with gastric cancer progression, but the role of epigenetic modifications remains unclear. We investigated methylation of the claudin‑3 promoter and expression profiles in gastric adenocarcinoma and their associations with clinicopathological characteristics and prognosis of the patients. A total of 122 patients with advanced gastric cancer [stage IIB‑IV, with lymph node (LN) metastasis] were enrolled. Each patient provided 4 tissue samples: normal gastric epithelium, intestinal metaplasia, primary tumor and metastatic LN. Claudin‑3 protein expression was examined by immunohistochemistry. Claudin‑3 promoter methylation was determined by methylation‑specific PCR and verified by bisulfite sequencing PCR. Claudin‑3 mRNA expression was measured by real‑time PCR in a subset of cases, and its correlation with protein expression was analyzed using Spearman correlation. Kaplan‑Meier survival analysis was performed (log‑rank test). Factors associated with survival were identified by Cox regression. The strong expression rate of claudin‑3 in intestinal metaplasia, primary tumor, metastatic LN and normal gastric epithelium was 91.8, 58.2, 30.3 and 13.9%, respectively. The promoter hypermethylation rate in intestinal metaplasia, primary tumor, normal gastric epithelium and metastatic LN was 5.7, 27.9, 36.9 and 49.2%, respectively. Claudin‑3 mRNA and protein expression were positively correlated (P<0.001) with normal gastric epithelium (rs=0.745), intestinal metaplasia (rs=0.876), primary gastric adenocarcinoma (rs=0.915) and metastatic LN (rs=0.819). Claudin‑3 mRNA expression was negatively correlated with claudin‑3 promoter methylation. Median patient survival was 38, 22 and 11 months in the hypomethylated, partially methylated and hypermethylated groups, respectively (P<0.001). Claudin‑3 promoter methylation status (HR: 5.67; 95% CI: 2.27‑14.17) but not claudin‑3 expression was an independent predictor of survival. Claudin‑3 promoter hypermethylation reduces claudin‑3 expression and independently predicts poor prognosis.
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1 

Catalano V, Labianca R, Beretta GD, Gatta G, de Braud F and Van Cutsem E: Gastric cancer. Gastric Rev Oncol Hematol. 71:127–164. 2009. View Article : Google Scholar

2 

Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI

4 

Maruyama K: The most important prognostic factors for gastric cancer patients: A study using univariate and multivariate analyses. Scand J Gastroenterol. 22:63–68. 1987. View Article : Google Scholar

5 

Huang L, Wu RL and Xu AM: Epithelial-mesenchymal transition in gastric cancer. Am J Transl Res. 7:2141–2158. 2015.PubMed/NCBI

6 

Turksen K and Troy TC: Junctions gone bad: Claudins and loss of the barrier in cancer. Biochim Biophys Acta. 1816:73–79. 2011.PubMed/NCBI

7 

Kwon MJ, Kim SH, Jeong HM, Jung HS, Kim SS, Lee JE, Gye MC, Erkin OC, Koh SS, Choi YL, et al: Claudin-4 overexpression is associated with epigenetic derepression in gastric carcinoma. Lab Invest. 91:1652–1667. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Zavala-Zendejas VE, Torres-Martinez AC, Salas-Morales B, Fortoul TI, Montano LF and Rendon-Huerta EP: Claudin-6, 7, or 9 overexpression in the human gastric adenocarcinoma cell line AGS increases its invasiveness, migration, and proliferation rate. Cancer Invest. 29:1–11. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Sanada Y, Oue N, Mitani Y, Yoshida K, Nakayama H and Yasui W: Down-regulation of the claudin-18 gene, identified through serial analysis of gene expression data analysis, in gastric cancer with an intestinal phenotype. J Pathol. 208:633–642. 2006. View Article : Google Scholar : PubMed/NCBI

10 

Wu YL, Zhang S, Wang GR and Chen YP: Expression transformation of claudin-1 in the process of gastric adenocarcinoma invasion. World J Gastroenterol. 14:4943–4948. 2008. View Article : Google Scholar : PubMed/NCBI

11 

Huang J, Zhang L, He C, Qu Y, Li J, Zhang J, Du T, Chen X, Yu Y and Liu B: Claudin-1 enhances tumor proliferation and metastasis by regulating cell anoikis in gastric cancer. Oncotarget. 6:1652–1665. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Satake S, Semba S, Matsuda Y, Usami Y, Chiba H, Sawada N, Kasuga M and Yokozaki H: Cdx2 transcription factor regulates claudin-3 and claudin-4 expression during intestinal differentiation of gastric carcinoma. Pathol Int. 58:156–163. 2008. View Article : Google Scholar : PubMed/NCBI

13 

Wang H and Yang X: The expression patterns of tight junction protein claudin-1, −3, and −4 in human gastric neoplasms and adjacent non-neoplastic tissues. Int J Clin Exp Pathol. 8:881–887. 2015.PubMed/NCBI

14 

Jung H, Jun KH, Jung JH, Chin HM and Park WB: The expression of claudin-1, claudin-2, claudin-3, and claudin-4 in gastric cancer tissue. J Surg Res. 167:e185–e191. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Okugawa T, Oshima T, Chen X, Hori K, Tomita T, Fukui H, Watari J, Matsumoto T and Miwa H: Down-regulation of claudin-3 is associated with proliferative potential in early gastric cancers. Dig Dis Sci. 57:1562–1567. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Matsuda Y, Semba S, Ueda J, Fuku T, Hasuo T, Chiba H, Sawada N, Kuroda Y and Yokozaki H: Gastric and intestinal claudin expression at the invasive front of gastric carcinoma. Cancer Sci. 98:1014–1019. 2007. View Article : Google Scholar : PubMed/NCBI

17 

Auclair G and Weber M: Mechanisms of DNA methylation and demethylation in mammals. Biochimie. 94:2202–2211. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Hahn-Strömberg V, Askari S, Ahmad A, Befekadu R and Nilsson TK: Expression of claudin 1, claudin 4, and claudin 7 in colorectal cancer and its relation with CLDN DNA methylation patterns. Tumour Biol. 39:10104283176975692017. View Article : Google Scholar : PubMed/NCBI

19 

Honda H, Pazin MJ, D'Souza T, Ji H and Morin PJ: Regulation of the CLDN3 gene in ovarian cancer cells. Cancer Biol Ther. 6:1733–1742. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Jiang L, Yang YD, Fu L, Xu W, Liu D, Liang Q, Zhang X, Xu L, Guan XY, Wu B, et al: CLDN3 inhibits cancer aggressiveness via Wnt-EMT signaling and is a potential prognostic biomarker for hepatocellular carcinoma. Oncotarget. 5:7663–7676. 2014. View Article : Google Scholar : PubMed/NCBI

21 

Agarwal R, Mori Y, Cheng Y, Jin Z, Olaru AV, Hamilton JP, David S, Selaru FM, Yang J, Abraham JM, et al: Silencing of claudin-11 is associated with increased invasiveness of gastric cancer cells. PLoS One. 4:e80022009. View Article : Google Scholar : PubMed/NCBI

22 

Lu S, Singh K, Mangray S, Tavares R, Noble L, Resnick MB and Yakirevich E: Claudin expression in high-grade invasive ductal carcinoma of the breast: Correlation with the molecular subtype. Mod Pathol. 26:485–495. 2013. View Article : Google Scholar : PubMed/NCBI

23 

VanGuilder HD, Vrana KE and Freeman WM: Twenty-five years of quantitative PCR for gene expression analysis. Biotechniques. 44:619–626. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Sonohara F, Inokawa Y, Hayashi M, Kodera Y and Nomoto S: Epigenetic modulation associated with carcinogenesis and prognosis of human gastric cancer. Oncol Lett. 13:3363–3368. 2017. View Article : Google Scholar : PubMed/NCBI

25 

Zheng H, Takahashi H, Murai Y, Cui Z, Nomoto K, Miwa S, Tsuneyama K and Takano Y: Pathobiological characteristics of intestinal and diffuse-type gastric carcinoma in Japan: An immunostaining study on the tissue microarray. J Clin Pathol. 60:273–277. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Pinheiro Ddo R, Ferreira WA, Barros MB, Araujo MD, Rodrigues-Antunes S and Borges Bdo N: Perspectives on new biomarkers in gastric cancer: Diagnostic and prognostic applications. World J Gastroenterol. 20:11574–11585. 2014. View Article : Google Scholar : PubMed/NCBI

27 

Ehrlich M and Lacey M: DNA hypomethylation and hemimethylation in cancer. Adv Exp Med Biol. 754:31–56. 2013. View Article : Google Scholar : PubMed/NCBI

28 

Mroz EA and Rocco JW: The challenges of tumor genetic diversity. Cancer. 123:917–927. 2017. View Article : Google Scholar : PubMed/NCBI

29 

Sun S and Li P: HMPL: A pipeline for identifying hemimethylation patterns by comparing two samples. Cancer Inform. 14 Suppl 2:S235–S245. 2015.

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Copy and paste a formatted citation
Spandidos Publications style
Zhang Z, Yu W, Chen S, Chen Y, Chen L and Zhang S: Methylation of the claudin‑3 promoter predicts the prognosis of advanced gastric adenocarcinoma. Oncol Rep 40: 49-60, 2018.
APA
Zhang, Z., Yu, W., Chen, S., Chen, Y., Chen, L., & Zhang, S. (2018). Methylation of the claudin‑3 promoter predicts the prognosis of advanced gastric adenocarcinoma. Oncology Reports, 40, 49-60. https://doi.org/10.3892/or.2018.6411
MLA
Zhang, Z., Yu, W., Chen, S., Chen, Y., Chen, L., Zhang, S."Methylation of the claudin‑3 promoter predicts the prognosis of advanced gastric adenocarcinoma". Oncology Reports 40.1 (2018): 49-60.
Chicago
Zhang, Z., Yu, W., Chen, S., Chen, Y., Chen, L., Zhang, S."Methylation of the claudin‑3 promoter predicts the prognosis of advanced gastric adenocarcinoma". Oncology Reports 40, no. 1 (2018): 49-60. https://doi.org/10.3892/or.2018.6411
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang Z, Yu W, Chen S, Chen Y, Chen L and Zhang S: Methylation of the claudin‑3 promoter predicts the prognosis of advanced gastric adenocarcinoma. Oncol Rep 40: 49-60, 2018.
APA
Zhang, Z., Yu, W., Chen, S., Chen, Y., Chen, L., & Zhang, S. (2018). Methylation of the claudin‑3 promoter predicts the prognosis of advanced gastric adenocarcinoma. Oncology Reports, 40, 49-60. https://doi.org/10.3892/or.2018.6411
MLA
Zhang, Z., Yu, W., Chen, S., Chen, Y., Chen, L., Zhang, S."Methylation of the claudin‑3 promoter predicts the prognosis of advanced gastric adenocarcinoma". Oncology Reports 40.1 (2018): 49-60.
Chicago
Zhang, Z., Yu, W., Chen, S., Chen, Y., Chen, L., Zhang, S."Methylation of the claudin‑3 promoter predicts the prognosis of advanced gastric adenocarcinoma". Oncology Reports 40, no. 1 (2018): 49-60. https://doi.org/10.3892/or.2018.6411
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