Quantitative Analysis of Cancer-associated Gene Methylation Connected to Risk Factors in Korean Colorectal Cancer Patients
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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, p16INK4a, 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 p16INK4a 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.
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, p16INK4a, 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 p16INK4a 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.
참고문헌 (36)
- Grady WM, "Genomic and epigenetic instability in colorectal cancer pathogenesis", Gastroenterology, 135(4), pp.1079~1099 (2008)
- Parkin DM, "Global cancer statistics", CA Cancer J Clin, 49(1), pp.33~64 (1999)
- Kim MS, "DNA methylation markers in colorectal cancer", Cancer Metastasis Rev, 29(1), pp.181~206 (2010)
- Nishisho I, "Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients", Science, 253(5020), pp.665~669 (1991)
- Vogelstein B, "Genetic alterations during colorectal-tumor development", N Engl J Med, 319(9), pp.525~532 (1988)
- Baylin SB, "DNA hypermethylation in tumorigenesis: epigenetics joins genetics", Trends Genet, 16(4), pp.168~174 (2000)
- Rashid A, "CpG island methylation in colorectal adenomas", Am J Pathol, 159(3), pp.1129~1135 (2001)
- Esteller M, "Analysis of adenomatous polyposis coli promoter hypermethylation in human cancer", Cancer Res, 60(16), pp.4366~4371 (2000)
- Herman JG, "Inactivation of the CDKN2", p16, Cancer Res, pp.1995, 55(20)[DOI]
- Rodriguez J, "Chromosomal instability correlates with genome-wide DNA demethylation in human primary colorectal cancers", Cancer Res, 66(17), pp.8462~8468 (2006)
- Feng Q, "DNA methylation in tumor and matched normal tissues from non-small cell lung cancer patients", Cancer Epidemiol Biomarkers Prev, 17(3), pp.645~654 (2008)
- Friedrich MG, "Detection of methylated apoptosis-associated genes in urine sediments of bladder cancer patients", Clin Cancer Res, 10(22), pp.7457~7465 (2004)
- Chen G, "Direct, real-time PCR (MethyLight) assay for methylation of O6-methylguanine-DNA methyltransferase promoter in glioma", Chin Med J (Engl), 122(11), pp.1342~1345 (2009)
- Eads CA, "MethyLight: a high-throughput assay to measure DNA methylation", Nucleic Acids Res, 28(8), pp.32~ (2000)
- Ogino S, "Precision and performance characteristics of bisulfite conversion and real-time PCR (MethyLight) for quantitative DNA methylation analysis", J Mol Diagn, 8(2), pp.209~217 (2006)
- Jin M, "Different histological types of non-small cell lung cancer have distinct folate and DNA methylation levels", Cancer Sci, 100(12), pp.2325~2330 (2009)
- Wolff EM, "RUNX3 methylation reveals that bladder tumors are older in patients with a history of smoking", Cancer Res, 68(15), pp.6208~6214 (2008)
- Hsu CY, "Interobserver reproducibility of MIB-1 labeling index in astrocytic tumors using different counting methods", Mod Pathol, 16(9), pp.951~957 (2003)
- Jones PA, "Cancer epigenetics comes of age", Nat Genet, 21(2), pp.163~167 (1999)
- Hiltunen MO, "Hypermethylation of the APC (adenomatous polyposis coli) gene promoter region in human colorectal carcinoma", Int J Cancer, 70(6), pp.644~648 (1997)
- Eads CA, "CpG island hypermethylation in human colorectal tumors is not associated with DNA methyltransferase overexpression", Cancer Res, 59(10), pp.2302~2306 (1999)
- Chen J, "Molecular analysis of APC promoter methylation and protein expression in colorectal cancer metastasis", Carcinogenesis, 26(1), pp.37~43 (2005)
- Araki Y, "Regulation of cyclooxygenase-2 expression by the Wnt and ras pathways", Cancer Res, 63(3), pp.728~734 (2003)
- Castells A, "Cyclooxygenase 2 expression in colorectal cancer with DNA mismatch repair deficiency", Clin Cancer Res, 12(6), pp.1686~1692 (2006)
- Lin SY, "Promoter CpG methylation of tumor suppressor genes in colorectal cancer and its relationship to clinical features", Oncol Rep, 11(2), pp.341~348 (2004)
- Burri N, "Methylation silencing and mutations of the p14ARF and p16INK4a genes in colon cancer", Lab Invest, 81(2), pp.217~229 (2001)
- Wiencke JK, "Aberrant methylation of p16INK4a in anatomic and gender-specific subtypes of sporadic colorectal cancer", Cancer Epidemiol Biomarkers Prev, 8(6), pp.501~506 (1999)
- Ishiguro A, "Influence of methylated p15 and p16 genes on clinicopathological features in colorectal cancer", J Gastroenterol Hepatol, 21(8), pp.1334~1339 (2006)
- Wagner KJ, "Frequent RASSF1A tumour suppressor gene promoter methylation in Wilms’ tumour and colorectal cancer", Oncogene, 21(47), pp.7277~7282 (2002)
- Xu XL, "Methylation profile of the promoter CpG islands of 31 genes that may contribute to colorectal carcinogenesis", World J Gastroenterol, 10(23), pp.3441~3454 (2004)
- Shen L, "MGMT promoter methylation and field defect in sporadic colorectal cancer", J Natl Cancer Inst, 97(18), pp.1330~1338 (2005)
- Toyota M, "CpG island methylator phenotype in colorectal cancer", Proc Natl Acad Sci U S A, 96(15), pp.8681~8686 (1999)
- Ruppenthal RD, "TWIST1 promoter methylation in primary colorectal carcinoma", Pathol Oncol Res, 17(4), pp.867~872 (2011)
- Okada T, "TWIST1 hypermethylation is observed frequently in colorectal tumors and its overexpression is associated with unfavorable outcomes in patients with colorectal cancer", Genes Chromosomes Cancer, 49(5), pp.452~462 (2010)
- El-Osta A, "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, 22(6), pp.1844~1857 (2002)
- Gulubova M, "Role of TGF-beta1, its receptor TGFbetaRII, and Smad proteins in the progression of colorectal cancer", Int J Colorectal Dis, 25(5), pp.591~599 (2010)
