The Clinical Study On The Peripheral Blood Methylated SEPT9 Gene Detection In The Diagnosis Of Colorectal Cancer And Adenoma

Part 1 Clinical significance of detecting peripheral blood methylated SEPT9 gene in the diagnosis of colorectal cancer and adenomaObjective To preliminary investigate the clinical significance of using methylated SEPT9 gene(m SEPT9)assay in diagnosis of colorectal cancer and adenoma.Methods The patients admitted to the First Affiliated Hospital of Soochow University from December 2016 to April 2017 were aged 18-80 years.There was no history of other malignant tumors,no surgery and radiotherapy and chemotherapy.All women were non-pregnant.A total of 189 eligible patients were enrolled.The average age was 57.81±12.35 years old.The patients were divided into three groups according to the results of colonoscopy and pathology.The normal control group(57 cases)had no obvious abnormalities under colonoscopy;Adenoma group(61 cases)included 20 cases of low-risk group and 41 cases of high-risk group,of which high-risk group of adenomas conformed to one of the following conditions: the largest diameter of lesions was more than 10 mm,with villous structure or high grade intraepithelial neoplasia;CRC group(71 cases)according to the AJCC Seventh Edition diagnostic criteria to determine the clinical stage.10 ml of peripheral blood was collected and m SEPT9 was detected by PCR fluorescence probe method.The positive rate of m SEPT9 was determined by Ct?41.0.Analysis of the gene expression in each subgroup and the relationship of its positive rate between different clinical features of CRC.Statistical analysis using SPSS 23.0,mapping m SEPT9 ROC curve diagnosis of colorectal cancer.Results(1)There was no positive results in the normal control group.The positive rate of m SEPT9 in adenoma group was 6.56%(4/61),with 10.00%(2/20)in low risk group and 4.88%(2/41)in advanced group.The positive rate of colorectal cancer group was 52.11%(37/71).The difference between colorectal cancer group and normal control group and adenoma group was statistically significant(?2 = 39.28,29.71,P <0.01).There was no significant difference between adenoma group and normal control group(?2 = 2.13,P> 0.05).There was no significant difference between low-risk adenomas and advanced adenomas(?2 = 0.043,P> 0.05).(2)Compared with the positive rate of m SEPT9 in different clinical features of colorectal cancer group,there was no significant difference among different gender,age,tumor location,lesion size and differentiation degree(?2 = 0.073,0.031,0.115,1.782,0.377,P> 0.05).In the presence or absence of lymph node metastasis and distant metastasis,the different clinical stages,the detection rates were significantly different.(?2 = 7.395,10.228,P <0.05 respectively).(3)The AUC value of m SEPT9 in diagnosing CRC was 0.831.Conclusions Detection of peripheral blood methylation SEPT9 gene in CRC diagnosis with high sensitivity and specificity.The detection rate is not related to the subjects' gender,age,tumor location,size and differentiation of lesions,but positively correlate with the progress of CRC.When used alone in adenoma diagnosis,its value may be limited.Part 2 Clinical significance of the detection of methylated SEPT9 gene in peripheral blood combined with tumor markers and fecal occult blood test in the diagnosis of colorectal cancer and adenomaObjective To investigate the clinical significance of detection of peripheral blood methylated SEPT9 gene(m SEPT9)combined with tumor markers and fecal occult blood test in the diagnosis of colorectal cancer and adenoma.Methods The data of five tumor markers,CEA,CA125,CA199,CA724 and CA211,were collected and the tumor markers were compared between groups by F test or rank sum test.The sensitivity and specificity of each tumor marker in diagnosing CRC were compared,then the tumor markers with high diagnostic efficiency were screened out.FIT results were further collected from patients enrolled in the study,combined with m SEPT9,tumor markers,FIT diagnosis of CRC and adenoma.Logistic regression was used to establish the regression equation.The m SEPT9,tumor markers,FIT and new variables were analyzed by ROC.The diagnostic value of m SEPT9,tumor markers and FIT alone and in combination in CRC and adenoma were compared.Results(1)A total of 135 enrolled patients had five tumor marker data,of which only the CEA level in the CRC group and the normal control group,adenoma group,the difference was statistically significant(P <0.05).The sensitivity of CEA in CRC group was 41.94%,and the specificity was 90%.(2)A total of 109 patients had complete m SEPT9,CEA and FIT data.The combined diagnosis of colorectal cancer was 97.67% with a specificity of 82.14%.Logistic regression equation was established as follows: Y = 1 / [1 + EXP(0.334 * m SEPT9 + 0.269 * CEA + 4.694 * FIT-0.027)].The sensitivity of combined diagnosis of low-risk adenomas and high-risk adenomas was 25.00% and 38.46%,respectively,with no significant difference(P <0.05).Conclusions Tumor markers alone in the diagnosis of colorectal cancer and adenoma is of little significance,combined use of five markers help to improve the detection rate of CRC.FIT alone diagnosis of CRC with high sensitivity and specificity,in the distinction between high-risk adenoma little effect.Combination of m SEPT9,CEA and FIT can improve the detection rate of CRC and high-risk adenoma.