Analysis of APC and IGFBP7 promoter gene methylation in Swedish and Vietnamese colorectal cancer patients

Dimberg,Jan; Hong,Thai  Trinh; Skarstedt,Marita; Löfgren,Sture; Zar,Niklas; Matussek,Andreas

doi:10.3892/ol.2012.967

Analysis of APC and IGFBP7 promoter gene methylation in Swedish and Vietnamese colorectal cancer patients

Authors:
- Jan Dimberg
- Thai Trinh Hong
- Marita Skarstedt
- Sture Löfgren
- Niklas Zar
- Andreas Matussek
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Affiliations: Department of Natural Science and Biomedicine, University College of Health Sciences, Jönköping, Sweden, Key Laboratory of Enzyme and Protein Technology, College of Science, Vietnam National University, Hanoi, Vietnam, Department of Clinical Microbiology, Ryhov County Hospital, Jönköping, Sweden, Department of Surgery, Ryhov County Hospital, Jönköping, Sweden, Department of Laboratory Services, Ryhov County Hospital, Jönköping, Sweden
Published online on: October 12, 2012 https://doi.org/10.3892/ol.2012.967
Pages: 25-30

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Abstract

The tumour suppressor gene adenomatous polyposis coli (APC) is a key component that drives colorectal carcinogenesis. The reported DNA methylation in the promoter of APC varies greatly among studies of colorectal cancer (CRC) in different populations. Insulin-like growth factor binding protein 7 (IGFBP7), also known as IGFBP‑related protein 1 (IGFBP-rP1), is expressed in various tissue types, including the lung, brain, prostate and gastrointestinal tract, and has been suggested to play a tumour suppressor role against colorectal carcinogenesis. Studies have indicated that IGFBP7 is inactivated by DNA methylation in human colon, lung and breast cancer. In the present study, we used the methylation‑specific polymerase chain reaction to study the methylation status of the APC and IGFBP7 gene promoters in cancerous and paired normal tissue to evaluate its impact on clinical factors and association with ethnicity, represented by Swedish and Vietnamese CRC patients. We also investigated the distribution of CpG islands and the CpG dinucleotide density of each CpG island in the regions which were the subject of our investigation. Overall, normal tissue from Swedish patients exhibited a significantly higher frequency of IGFBP7 gene methylation in comparison with that of Vietnamese patients. Moreover, a significantly higher number of cancer tissues from Vietnamese individuals showed higher levels of methylation versus the paired normal tissue compared with that of Swedish patients. When we studied the methylation in cancer compared with the matched normal tissue in individuals, we found that a significantly higher number of Vietnamese patients had a higher degree of IGFBP7 gene methylation in cancer versus matched normal tissue in comparison with Swedish patients. Taken together, our results suggest that the methylation of the APC and IGFBP7 gene promoter region in cancerous tissue, in combination with the predominance of methylation in normal tissue, may serve as a prognostic factor in CRC patients.

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1	Miyoshi Y, Nagase H, Ando H, Horii A, Ichii S, Nakatsuru S, Aoki T, Miki Y, Mori T and Nakamura Y: Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene. Hum Mol Genet. 1:229–233. 1992. View Article : Google Scholar : PubMed/NCBI
2	Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B and Kinzler KW: Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science. 275:1787–1790. 1997. View Article : Google Scholar : PubMed/NCBI
3	Schneikert J and Behrens J: The canonical Wnt signalling pathway and its APC partner in colon cancer development. Gut. 56:417–425. 2007. View Article : Google Scholar : PubMed/NCBI
4	Durai R, Yang W, Gupta S, Seifalian AM and Winslet MC: The role of the insulin-like growth factor system in colorectal cancer: review of current knowledge. Int J Colorectal Dis. 20:203–220. 2005. View Article : Google Scholar : PubMed/NCBI
5	Degeorges A, Wang F, Frierson HF Jr, Seth A and Sikes RA: Distribution of IGFBP-rP1 in normal human tissues. J Histochem Cytochem. 48:747–754. 2000. View Article : Google Scholar : PubMed/NCBI
6	Burger AM, Leyland-Jones B, Banerjee K, Spyropoulos DD and Seth AK: Essential roles of IGFBP-3 and IGFBP-rP1 in breast cancer. Eur J Cancer. 41:1515–1527. 2005. View Article : Google Scholar : PubMed/NCBI
7	Sato Y, Chen Z and Miyazaki K: Strong suppression of tumor growth by insulin-like growth factor-binding protein-related protein 1/tumor-derived cell adhesion factor/mac25. Cancer Sci. 98:1055–1063. 2007. View Article : Google Scholar : PubMed/NCBI
8	Georges RB, Adwan H, Hamdi H, Hielscher T, Linnemann U and Berger MR: The insulin-like growth factor binding proteins 3 and 7 are associated with colorectal cancer and liver metastasis. Cancer Biol Ther. 12:69–79. 2011. View Article : Google Scholar : PubMed/NCBI
9	Ruan WJ, Lin J, Xu EP, Xu FY, Ma Y, Dengh H, Huang Q, Lv BJ, Hu H, Cui J, Di MJ, Dong JK and Lai MD: IGFBP7 plays a potential tumor suppressor role against colorectal carcinogenesis with its expression associated with DNA hypomethylation of exon 1. J Zhejiang Univ Sci B. 7:929–932. 2006. View Article : Google Scholar : PubMed/NCBI
10	Ruan W, Xu E, Xu F, Ma Y, Deng H, Huang Q, Lv B, Hu H, Lin J, Cui J, Di M, Dong J and Lai M: IGFBP7 plays a potential tumor suppressor role in colorectal carcinogenesis. Cancer Biol Ther. 6:354–359. 2007. View Article : Google Scholar : PubMed/NCBI
11	Ye F, Chen Y, Knösel T, Schluns K, Pacyna-Gengelbach M, Deutschmann N, Lai M and Petersen I: Decreased expression of insulin-like growth factor binding protein 7 in human colorectal carcinoma is related to DNA methylation. J Cancer Res Clin Oncol. 133:305–314. 2007. View Article : Google Scholar : PubMed/NCBI
12	Mälarstig A, Wågsäter D, Löfgren S, Hugander A, Zar N and Dimberg J: Tumor-derived adhesion factor in colorectal cancer. Mol Med Rep. 2:971–976. 2009.
13	Kondo Y and Issa JP: Epigenetic changes in colorectal cancer. Cancer Metastasis Rev. 23:29–39. 2004. View Article : Google Scholar
14	Venkatachalam R, Ligtenberg MJ, Hoogerbrugge N, de Bruijn DR, Kuiper RP and Geurts van Kessel A: The epigenetics of (hereditary) colorectal cancer. Cancer Genet Cytogenet. 203:1–6. 2010. View Article : Google Scholar : PubMed/NCBI
15	Jones PA and Baylin SB: The epigenomics of cancer. Cell. 128:683–692. 2007. View Article : Google Scholar : PubMed/NCBI
16	Naghibalhossaini F, Zamani M, Mokarram P, Khalili I, Rasti M and Mostafavi-Pour Z: Epigenetic and genetic analysis of WNT signaling pathway in sporadic colorectal cancer patients from Iran. Mol Biol Rep. 39:6171–6178. 2012. View Article : Google Scholar : PubMed/NCBI
17	Esteller M, Sparks A, Toyota M, Sanchez-Cespedes M, Capella G, Peinado MA, Gonzales S, Tarafa G, Sidransky D, Meltzer SJ, Baylin SB and Herman JG: Analysis of adenomatous polyposis coli promoter hypermethylation in human cancer. Cancer Res. 60:4366–4371. 2000.PubMed/NCBI
18	Lee S, Hwang KS, Lee HJ, Kim JS and Kang GH: Aberrant CpG island hypermethylation of multiple genes in colorectal neoplasia. Lab Invest. 84:884–893. 2004. View Article : Google Scholar : PubMed/NCBI
19	Lee BB, Lee EJ, Jung EH, Chun HK, Chang DK, Song SY, Park J and Kim DK: Aberrant methylation of APC, MGMT, RASSF2A and Wif-1 genes in plasma as a biomarker for early detection of colorectal cancer. Clin Cancer Res. 15:6185–6191. 2009. View Article : Google Scholar : PubMed/NCBI
20	Chen SP, Chiu SC, Wu CC, Lin SZ, Kang JC, Chen YL, Lin PC, Pang CY and Harn HJ: The association of methylation in the promoter of APC and MGMT and the prognosis of Taiwanese CRC patients. Genet Test Mol Biomarkers. 13:67–71. 2009. View Article : Google Scholar : PubMed/NCBI
21	Lin J, Lai M, Huang Q, Ruan W, Ma Y and Cui J: Reactivation of IGFBP7 by DNA demethylation inhibits human colon cancer cell growth in vitro. Cancer Biol Ther. 7:1896–1900. 2008. View Article : Google Scholar : PubMed/NCBI
22	Chen Y, Cui T, Knösel T, Yang L, Zöller K and Petersen I: IGFBP7 is a p53 target gene inactivated in human lung cancer by DNA hypermethylation. Lung Cancer. 73:38–44. 2011. View Article : Google Scholar : PubMed/NCBI
23	Smith P, Nicholson LJ, Syed N, Payne A, Hiller L, Garrone O, Occelli M, Gasco M and Crook T: Epigenetic inactivation implies independent functions for insulin-like growth factor binding protein (IGFBP)-related protein 1 and related IGFBPL1 in inhibiting breast cancer phenotypes. Clin Cancer Res. 13:4061–4068. 2007. View Article : Google Scholar
24	Herman JG, Graff JR, Myöhänen S, Nelkin BD and Baylin SB: Methylation-specific PCR: A novel PCR assay methylation status of CpG islands. Proc Natl Acad Sci USA. 93:9821–9826. 1996. View Article : Google Scholar : PubMed/NCBI
25	Li LC and Dahiya R: MethPrimer: designing primers for methylation PCRs. Bioinformatics. 18:1427–1431. 2002. View Article : Google Scholar : PubMed/NCBI
26	Rice P, Longden I and Bleasby A: EMBOSS: The European Molecular Biology Open Software Suite. Trends Genet. 16:276–277. 2000. View Article : Google Scholar : PubMed/NCBI
27	Davuluri RV, Grosse I and Zhang MQ: Computational identification of promoters and first exons in the human genome. Nat Genet. 29:412–417. 2001. View Article : Google Scholar : PubMed/NCBI
28	Prestridge DS: Predicting Pol II promoter sequences using transcription factor binding sites. J Mol Biol. 249:923–932. 1995. View Article : Google Scholar : PubMed/NCBI
29	Clément G, Bosman FT, Fontolliet C and Benhattar J: Monoallelic methylation of the APC promoter is altered in normal gastric mucosa associated with neoplastic lesions. Cancer Res. 64:6867–6873. 2004.PubMed/NCBI
30	Sakamoto Y, Kitazawa R, Maeda S and Kitazawa S: Methylation of CpG loci in 5′ -flanking region alters steady-state expression of adenomatous polyposis coli gene in colon cancer cell lines. J Cell Biol. 80:415–423. 2001.
31	Lind GE, Thorstensen L, Løvig T, Meling GI, Hamelin R, Rognum TO, Esteller M and Lothe RA: A CpG island hypermetylation profile of primary colorectal carcinomas and colon cancer cell lines. Mol Cancer. 3:282004. View Article : Google Scholar : PubMed/NCBI
32	Adachi Y, Itoh F, Yamamoto H, Arimura Y, Kikkawa-Okabe Y, Miyazaki K, Carbone DP and Imai K: Expression of angiomodulin (tumor-derived adhesion factor/mac25) in invading tumor cells correlates with poor prognosis in human colorectal cancer. Int J Cancer. 95:216–222. 2001. View Article : Google Scholar : PubMed/NCBI
33	Lin J, Lai M, Huang Q, Ma Y, Cui J and Ruan W: Methylation patterns of IGFBP7 in colon cancer cell lines are associated with levels of gene expression. J Pathol. 212:83–90. 2007. View Article : Google Scholar : PubMed/NCBI
34	Nakajima T, Maekita T, Oda I, Gotoda T, Yamamoto S, Umemura S, Ichinose M, Sugimura T, Ushijima T and Saito D: Higher methylation levels in gastric mucosae significantly correlate with higher risk of gastric cancer. Cancer Epidemiol Biomarkers Prev. 15:2317–2321. 2006. View Article : Google Scholar : PubMed/NCBI
35	Shen L, Kondo Y, Rosner GL, Xiao L, Hernandez NS, Vilaythong J, Houlihan PS, Krouse RS, Prasad AR, Einspahr JG, Buckmeier J, Alberts DS, Hamilton SR and Issa JPJ: MGMT promoter methylation and field defect in sporadic colorectal cancer. J Natl Cancer Inst. 97:1330–1338. 2005. View Article : Google Scholar : PubMed/NCBI
36	Issa JP, Ahuja N, Toyota M, Bronner MP and Brentnall TA: Accelerated age-related CpG island methylation in ulcerative colitis. Cancer Res. 61:3573–3577. 2001.PubMed/NCBI
37	Anh PT and Duc NB: The situation with cancer control in Vietnam. Jpn J Clin Oncol. 32(Suppl): S92–S97. 2002. View Article : Google Scholar : PubMed/NCBI
38	Sung JJ, Lau JY, Young GP, Sano Y, Chiu HM, Byeon JS, Yeoh KG, Goh KL, Sollano J, Rerknimitr R, Matsuda T, Wu KC, Ng S, Leung SY, Makharia G, Chong VH, Ho KY, Brooks D, Lieberman DA and Chan FK; Asia Pacific Working Group on Colorectal Cancer: Asia Pacific consensus recommendations for colorectal cancer screening. Gut. 57:1166–1176. 2008. View Article : Google Scholar : PubMed/NCBI