Analysis On The CpG Island Methylator Phenotype(CIMP) Of Colorectal Cancer In Chinese Population

Objective CpG Island Methylator Phenotype (CIMP) is a kind of colorectal cancer type possessing different clinical characteristics and molecular characteristics, which involves multiple gene loci methylation. In recent years, it is widely believed that the CIMP plays an important role in the mechanism of the occurrence and development of many malignant tumors including colorectal cancer, and it many closely related to the clinical and pathological features of colorectal cancer. Therefore,an in-depth study of the CIMP and the exploration of the occurrence and development mechanism of tumor has very important significance for early diagnosis and treatment to colorectal cancer? as well as improve the prognosis of patients. At present, the developed countries in Europe and America carried out many of research on the CIMP of colorectal cancer population, due to the technical methods and detection of different genes, the detection rate of CIMP is about 17%-30%; and CIMP positive colorectal cancer tend to occur in the proximal colon, the elder and female patients, tissue type differentiation tendency is not obviously. At present, the research on the CIMP of Chinese population colorectal cancer is inadequate, the detection rate and the relationships between CIMP and pathological features is still insufficient. So the research on a large sample of colorectal cancer in Chinese population is very necessary. Some scholars in the study found that the realtime fluorescence quantitative PCR can detect CIMP rapidly and accurately, and they proposed five genes (CACNA1G, CDKN2A, CRABPI, MLH1, and NEUROG1) methylation as a detection biomarker for the CIMP. The aim of this study is to use the realtime fluorescence quantitative PCR to detect the methylation staus of the five genes (CACNA1G, CDKN2A, CRABP1,MLH1 and NEUROG1) in colorectal cancer, judge the CpG island methylator phenotype (CIMP) positive rate in colorectal cancer samples of Chinese population, and research the relationship between the clinical pathological features of sporadic colorectal cancer and CIMP, and the differences with foreign population, thus to explore the occurrence and development mechanism of CpG island methylator phenotype, in order to facilitate more in-depth in the tumor pathogenesis, and to provide scientific basis for individual treatment of Chinese population colorectal cancer.Methods Using realtime fluorescence quantitative PCR technique to detect five gene promoter (CACNA1G, CDKN2A, CRABP1, MLH1, and NEUROG1) methylation status in 100 cases of colorectal cancer tissue cells, to determine the CpG island methylator phenotype (CIMP) positive rate. Using SPSS 17.0 statistical software to analysis the results of the data,using analysis method of statistical analysis the chi square test.Results1. When we defined CpG island methylator phenotype (CIMP) as having≥3/5 methylated loci,51 cases in 100 cases of tumor cells is CIMP, the positive rate was 51%.2. There was a correlation between CIMP and tumor tissue differentiation type (from highly to poorly differentiated),the difference was statistically significant (P<0.0 5), but gender, age, tumor location, tumor TNM stage, depth of invasion, mucinous adenocarcinoma, adenoma, regional lymph node metastasis, neural invasion, vascul ar invasion, distant metastasis all have no significant correlation (P>0.05).Conclusions1. Using realtime fluorescence quantitative PCR technique can rapidly, effectively and accurately detect the CpG island methylator phenotype of DNA.2. We found that by detecting the mentioned 5 gene methylation status, the positive rate of the CpG island methylator phenotype of the 100 cases of colorectal cancer (51%) were significantly higher than those of previous similar studies of Western population (17%). Suggesting Chinese population colorectal cancer may have a higher CIMP positive rate.3. CpG island methylator phenotype positive sporadic colorectal cancer of Chinese po pulation has the characteristics of tendency in the low differentiated adenocarcino ma. CIMP was not founded related to gender, age, tumor location, tumor TNM sta ge, depth of invasion, mucinous adenocarcinoma, adenoma, regional lymph node m etastasis, neural invasion, vascular invasion, and distant metastasis. This is different from the result of previous similar studies of Western population:"CIMP was s ignificantly associated with female sex", suggesting the CIMP positive colorectal cancer of Chinese population may have distinct clinicopathologic characteristics.