DOI QR코드

DOI QR Code

Quantitative Analysis of Cancer-associated Gene Methylation Connected to Risk Factors in Korean Colorectal Cancer Patients

  • Kang, Ho-Jin (Department of Preventive Medicine, Dong-A University College of Medicine) ;
  • Kim, Eun-Jeong (Department of Preventive Medicine, Dong-A University College of Medicine) ;
  • Kim, Byoung-Gwon (Department of Preventive Medicine, Dong-A University College of Medicine) ;
  • You, Chang-Hun (Department of Preventive Medicine, Dong-A University College of Medicine) ;
  • Lee, Sang-Yong (Institute of Forensic Medicine, Pusan National University School of Medicine) ;
  • Kim, Dong-Il (Department of Occupational Medicine, Kangbuk Samsung Hospital) ;
  • Hong, Young-Seoub (Department of Preventive Medicine, Dong-A University College of Medicine)
  • Received : 2011.09.26
  • Accepted : 2012.03.14
  • Published : 2012.07.31

Abstract

Objectives: The purpose of this paper was to elucidate the potential methylation levels of adjacent normal and cancer tissues by comparing them with normal colorectal tissues, and to describe the correlations between the methylation and clinical parameters in Korean colorectal cancer (CRC) patients. Methods: Hypermethylation profiles of nine genes (RASSF1, APC, $p16^{INK4a}$, Twist1, E-cadherin, TIMP3, Smad4, COX2, and ABCB1) were examined with 100 sets of cancer tissues and 14 normal colorectal tissues. We determined the hypermethylation at a given level by a percent of methylation ratio value of 10 using quantitative methylation real-time polymerase chain reaction. Results: Nine genes' hypermethylation levels in Korean CRC patient tissues were increased more higher than normal colorectal tissues. However, the amounts of $p16^{INK4a}$ and E-cadherin gene hypermethylation in normal and CRC tissues were not significantly different nor did TIMP3 gene hypermethylation in adjacent normal and cancer tissues differ significantly. The hypermethylation of TIMP3, Ecadherin, ABCB1, and COX2 genes among other genes were abundantly found in normal colorectal tissues. The hypermethylation of nine genes' methylation in cancer tissues was not significantly associated with any clinical parameters. In Cohen's kappa test, it was moderately observed that RASSF1 was related with E-cadherin, and Smad4 with ABCB1 and COX2. Conclusions: This study provides evidence for different hypermethylation patterns of cancer-associated genes in normal and CRC tissues, which may serve as useful information on CRC cancer progression.

Keywords

References

  1. Grady WM, Carethers JM. Genomic and epigenetic instability in colorectal cancer pathogenesis. Gastroenterology 2008; 135(4):1079-1099.
  2. Parkin DM, Pisani P, Ferlay J. Global cancer statistics. CA Cancer J Clin 1999;49(1):33-64.
  3. Kim MS, Lee J, Sidransky D. DNA methylation markers in colorectal cancer. Cancer Metastasis Rev 2010;29(1):181-206.
  4. Nishisho I, Nakamura Y, Miyoshi Y, Miki Y, Ando H, Horii A, et al. Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science 1991;253(5020):665-669.
  5. Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, et al. Genetic alterations during colorectal-tumor development. N Engl J Med 1988;319(9):525-532.
  6. Baylin SB, Herman JG. DNA hypermethylation in tumorigenesis: epigenetics joins genetics. Trends Genet 2000;16(4):168-174.
  7. Rashid A, Shen L, Morris JS, Issa JP, Hamilton SR. CpG island methylation in colorectal adenomas. Am J Pathol 2001;159(3): 1129-1135.
  8. Esteller M, Sparks A, Toyota M, Sanchez-Cespedes M, Capella G, Peinado MA, et al. Analysis of adenomatous polyposis coli promoter hypermethylation in human cancer. Cancer Res 2000;60(16):4366-4371.
  9. Herman JG, Merlo A, Mao L, Lapidus RG, Issa JP, Davidson NE, et al. Inactivation of the CDKN2/p16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers. Cancer Res 1995;55(20):4525-4530.
  10. Rodriguez J, Frigola J, Vendrell E, Risques RA, Fraga MF, Morales C, et al. Chromosomal instability correlates with genome- wide DNA demethylation in human primary colorectal cancers. Cancer Res 2006;66(17):8462-8468.
  11. Feng Q, Hawes SE, Stern JE, Wiens L, Lu H, Dong ZM, et al. DNA methylation in tumor and matched normal tissues from nonsmall cell lung cancer patients. Cancer Epidemiol Biomarkers Prev 2008;17(3):645-654.
  12. Friedrich MG, Weisenberger DJ, Cheng JC, Chandrasoma S, Siegmund KD, Gonzalgo ML, et al. Detection of methylated apoptosis-associated genes in urine sediments of bladder cancer patients. Clin Cancer Res 2004;10(22):7457-7465.
  13. Chen G, Wu X, Yao Y, Zhou LF, Mao Y. Direct, real-time PCR (MethyLight) assay for methylation of O6-methylguanine-DNA methyltransferase promoter in glioma. Chin Med J (Engl) 2009;122(11):1342-1345.
  14. Eads CA, Danenberg KD, Kawakami K, Saltz LB, Blake C, Shibata D, et al. MethyLight: a high-throughput assay to measure DNA methylation. Nucleic Acids Res 2000;28(8):E32.
  15. Ogino S, Kawasaki T, Brahmandam M, Cantor M, Kirkner GJ, Spiegelman D, et al. Precision and performance characteristics of bisulfite conversion and real-time PCR (MethyLight) for quantitative DNA methylation analysis. J Mol Diagn 2006; 8(2):209-217.
  16. Jin M, Kawakami K, Fukui Y, Tsukioka S, Oda M, Watanabe G, et al. Different histological types of non-small cell lung cancer have distinct folate and DNA methylation levels. Cancer Sci 2009;100(12):2325-2330.
  17. Wolff EM, Liang G, Cortez CC, Tsai YC, Castelao JE, Cortessis VK, et al. RUNX3 methylation reveals that bladder tumors are older in patients with a history of smoking. Cancer Res 2008; 68(15):6208-6214.
  18. Hsu CY, Ho DM, Yang CF, Chiang H. Interobserver reproducibility of MIB-1 labeling index in astrocytic tumors using different counting methods. Mod Pathol 2003;16(9):951-957.
  19. Jones PA, Laird PW. Cancer epigenetics comes of age. Nat Genet 1999;21(2):163-167.
  20. Hiltunen MO, Alhonen L, Koistinaho J, Myohanen S, Paakkonen M, Marin S, et al. Hypermethylation of the APC (adenomatous polyposis coli) gene promoter region in human colorectal carcinoma. Int J Cancer 1997;70(6):644-648.
  21. Eads CA, Danenberg KD, Kawakami K, Saltz LB, Danenberg PV, Laird PW. CpG island hypermethylation in human colorectal tumors is not associated with DNA methyltransferase overexpression. Cancer Res 1999;59(10):2302-2306.
  22. Chen J, Rocken C, Lofton-Day C, Schulz HU, Muller O, Kutzner N, et al. Molecular analysis of APC promoter methylation and protein expression in colorectal cancer metastasis. Carcinogenesis 2005;26(1):37-43.
  23. Araki Y, Okamura S, Hussain SP, Nagashima M, He P, Shiseki M, et al. Regulation of cyclooxygenase-2 expression by the Wnt and ras pathways. Cancer Res 2003;63(3):728-734.
  24. Castells A, Paya A, Alenda C, Rodriguez-Moranta F, Agrelo R, Andreu M, et al. Cyclooxygenase 2 expression in colorectal cancer with DNA mismatch repair deficiency. Clin Cancer Res 2006;12(6):1686-1692.
  25. Lin SY, Yeh KT, Chen WT, Chen HC, Chen ST, Chiou HY, et al. Promoter CpG methylation of tumor suppressor genes in colorectal cancer and its relationship to clinical features. Oncol Rep 2004;11(2):341-348.
  26. Burri N, Shaw P, Bouzourene H, Sordat I, Sordat B, Gillet M, et al. Methylation silencing and mutations of the p14ARF and p16INK4a genes in colon cancer. Lab Invest 2001;81(2):217-
  27. Wiencke JK, Zheng S, Lafuente A, Lafuente MJ, Grudzen C, Wrensch MR, et al. Aberrant methylation of p16INK4a in anatomic and gender-specific subtypes of sporadic colorectal cancer. Cancer Epidemiol Biomarkers Prev 1999;8(6):501-506.
  28. Ishiguro A, Takahata T, Saito M, Yoshiya G, Tamura Y, Sasaki M, et al. Influence of methylated p15 and p16 genes on clinicopathological features in colorectal cancer. J Gastroenterol Hepatol 2006;21(8):1334-1339.
  29. Wagner KJ, Cooper WN, Grundy RG, Caldwell G, Jones C, Wadey RB, et al. Frequent RASSF1A tumour suppressor gene promoter methylation in Wilms' tumour and colorectal cancer. Oncogene 2002;21(47):7277-7282.
  30. Xu XL, Yu J, Zhang HY, Sun MH, Gu J, Du X, et al. Methylation profile of the promoter CpG islands of 31 genes that may contribute to colorectal carcinogenesis. World J Gastroenterol 2004;10(23):3441-3454.
  31. Shen L, Kondo Y, Rosner GL, Xiao L, Hernandez NS, Vilaythong J, et al. MGMT promoter methylation and field defect in sporadic colorectal cancer. J Natl Cancer Inst 2005;97(18):1330-1338.
  32. Toyota M, Ahuja N, Ohe-Toyota M, Herman JG, Baylin SB, Issa JP. CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci U S A 1999;96(15):8681-8686.
  33. Ruppenthal RD, Nicolini C, Filho AF, Meurer R, Damin AP, Rohe A, et al. TWIST1 promoter methylation in primary colorectal carcinoma. Pathol Oncol Res 2011;17(4):867-872.
  34. Okada T, Suehiro Y, Ueno K, Mitomori S, Kaneko S, Nishioka M, et al. TWIST1 hypermethylation is observed frequently in colorectal tumors and its overexpression is associated with unfavorable outcomes in patients with colorectal cancer. Genes Chromosomes Cancer 2010;49(5):452-462.
  35. El-Osta A, Kantharidis P, Zalcberg JR, Wolffe AP. Precipitous release of methyl-CpG binding protein 2 and histone deacetylase 1 from the methylated human multidrug resistance gene (MDR1) on activation. Mol Cell Biol 2002;22(6):1844-1857.
  36. Gulubova M, Manolova I, Ananiev J, Julianov A, Yovchev Y, Peeva K. Role of TGF-beta1, its receptor TGFbetaRII, and Smad proteins in the progression of colorectal cancer. Int J Colorectal Dis 2010;25(5):591-599.

Cited by

  1. Hypermethylation ofTWIST1andNID2in Tumor Tissues and Voided Urine in Urinary Bladder Cancer Patients vol.32, pp.7, 2012, https://doi.org/10.1089/dna.2013.2030
  2. Role of CDH1 Promoter Methylation in Colorectal Carcinogenesis: A Meta-Analysis vol.33, pp.7, 2014, https://doi.org/10.1089/dna.2013.2291
  3. Promoter Methylation of the RASSF1A Gene may Contribute to Colorectal Cancer Susceptibility: A Meta‐Analysis of Cohort Studies vol.78, pp.3, 2014, https://doi.org/10.1111/ahg.12059
  4. RETRACTED ARTICLE: Aberrant promoter methylation of RASSF1A gene may be correlated with colorectal carcinogenesis: a meta-analysis vol.41, pp.6, 2014, https://doi.org/10.1007/s11033-014-3267-6
  5. Meta-analysis of the association between APC promoter methylation and colorectal cancer vol.8, pp.None, 2012, https://doi.org/10.2147/ott.s75827
  6. APC hypermethylation for early diagnosis of colorectal cancer: a meta-analysis and literature review vol.8, pp.28, 2012, https://doi.org/10.18632/oncotarget.17576
  7. A novel discriminating colorectal cancer model for differentiating normal and tumor tissues vol.10, pp.11, 2012, https://doi.org/10.2217/epi-2018-0063
  8. Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health vol.10, pp.None, 2018, https://doi.org/10.1186/s13148-018-0558-0
  9. KLHL22 Regulates the EMT and Proliferation in Colorectal Cancer Cells in Part via the Wnt/β-Catenin Signaling Pathway vol.12, pp.None, 2012, https://doi.org/10.2147/cmar.s252232