The Application Of SEPT9and NDRG4Gene Methylation Diagnosis In Colorectal Cancer

ObjectiveThe colorectal carcinoma incidence is increasing rapidly in our country in recently20years. A lot of clinical researchs demonstrated that early diagnosis ofcolorectal carcinoma can save patients’ life. Howerver, there are not anone-invasive methods to screen early colorectal carcinoma until now. DNAmethylation is an early epigenetic event during carcinogenesis and abnormalmehtylation can be as a tumor marker for diagnosis of cancer. The SEPT9andNDRG4gene methylation happened frequently in colorectal carcinoma tissuewere reported, wich indicate that abnormal methylation of both genes from stool,peripheral blood and urine can be used to detect early colorectal cancer. Toinvestigate the values in diagnosis of colorectal cancer by analysis of SEPT9andNDRG4genes methylation in stool, urine and peripheral blood DNA, we makethis resarch.Methods:Nity-nine cases of colorectal carcinoma hospitalized in general surgery andhepatobiliary surgery department of our hospital during2010-2011years wereseleted as experimental group. All of cases were confirmed by pathology. At thesame time,64none-cancer cases with age matched were selected as control group.All patients are required to not receive chemotherapy, radiotherapy or otheranti-cancer therapy before surgery. The DNA from cancer tissues, para-cancertissues, peripheral blood, stool and urine was got and kept in refrigerator. Thecancer tissues, para-cancer tissues and stool SEPT9gene methylation weredetected by nMSP and DHPLC. The NDRG4gene methylation were detected bynested methylation specific PCR in colorectal cancer tissues, para-cancer tissues， stool DNA, urine DNA and peripheral blood DNA. Statistical analysis: all thedata were analyzed with SPSS13.0statistics software.The statistical significancewas defined as P<0.05.Results1. Among87colorectal cancers, SEPT9gene methylation was found in80.5%(70/87) of colorectal carcinoma and8.0%(7/87) of para-carcinoma tissuesrespectively. The sensitivity and specificity of SEPT9were80.5%and91.9%respectively, and the stool DNA almost has similar sensitivity as cancer tissues indiagnosis of colorectal cancer. The methylation of SEPT9is significant associatedwih elderly with more than65years old and right colon cancer.2. Among84colorectal cancers, NDRG4gene methylation was found in81%ofcancer tissues and8.3%of para-cancer tissues respectively. The sensitivity andspecify of NDRG4for diagnosis of colorectal cancer were81%and91.7%respectively, and the stool and urine NDRG4better sensitivitily and specificitilyin diagnosis of colorectal cancer.3. The stool DNA of SEPT9and NDRG4gene methylation detection can improvethe sensitivity of colorectal cancer.Conclusion1. The abnormal methylation of SEPT9was happened frequently in colorectalcancer, especilly in elderly and right colon cancer; hypermethylaion ofSEPT9gene mehylation in stool DNA can be used as a candidate of tumormarker for early diagnosis of colorectal cancer.2. Hypermethylaion of NDRG4gene mehylation in stool and urine DNA can beused as candidates of tumor marker for early diagnosis of colorectal cancer.3. The stool DNA of SEPT9and NDRG4gene methylation detection is expectedto become a new means of CRC screening.