粪便和血浆四基因甲基化联检用于结直肠癌诊断的临床价值

Clinical value of four-gene methylation in feces and plasma for the diagnosis of colorectal cancer

目的:探讨粪便和血浆隔膜蛋白9(Septin9)、支链氨基酸氨基转移酶1(BCAT1)、IKAROS家族锌指1(IKZF1)、黏结蛋白聚糖2(SDC2)基因甲基化多联检在结直肠癌的诊断临床效用。方法:选取2023年1月至2023年10月宁波大学附属第一医院收集30例结直肠癌患者样本为实验组,30例健康志愿者样本为对照组,使用高灵敏度MS-PCR方法检测粪便和血浆样本Septin9、BCAT1、IKZF1、SDC2基因启动子区甲基化状况,以评估其用于结直肠癌诊断的灵敏度和特异性,通过ROC曲线分析检测的临床效用,阳性率比较采用卡方检验或Fisher确切概率检验。结果:粪便样本联合检测灵敏度为86.6%,特异性为90.0%[95%可信区间(CI):0.805~0.989];血浆样本联合检测灵敏度为83.3%,特异性为89.3%(95%CI:0.715~0.951)。粪便样本Septin9、BCAT1、IKZF1、SDC2四基因甲基化检测转阴率分别是78.5%、100%、100%、90.9%;血浆样本四基因甲基化检测转阴率分别是77%、100%、70%、100%。结论:四基因甲基化标志物联检用于结直肠癌诊断临床效用优于粪便隐血检测,粪便样本临床效用优于血浆样本,术前术后检测结果差异显著。

Objective:Study on the clinical utility of multi-site detection of methylation of genes Septin9,Branched-chain Amino Acid Transaminase 1(BCAT1),IKAROS Family Zinc Finger 1(IKZF1),Syndecan-2(SDC2)in feces and plasma for the diagnosis of colorectal cancer,and exploration of the clinical application prospects of multi-target combined detection for postoperative minimal residual detection and recurrence monitoring in colorectal cancer.Methods:Many feces and plasma samples were collected in the First Affiliated Hospital of Ningbo University from January 2023 to October 2023,with colorectal cancer patients as experimental group and healthy volunteers as control group.Highly sensitive MS-PCR method was used to detect the methylation status of Septin9,BCAT1,IKZF1 and SDC2 gene promoter in fecal and plasma samples in order to evaluate its sensitivity and specificity in the diagnosis of colorectal cancer.The clinical efficacy of detection was analyzed by ROC curve.The positive rate was compared by chi-square test or Fisher exact probability test.Results:The sensitivity of joint detection in fecal samples is 86.6%with a specificity of 90%.The sensitivity of joint detection in plasma samples is 83.3%with a specificity of 89.3%.Postoperative methylation test negative rates for genes Septin9,BCAT1,IKZF1,SDC2 in fecal samples are 78.5%,100%,100%,and 90.9%respectively.In postoperative plasma samples,the methylation test negative rates for genes Septin9,BCAT1,IKZF1,SDC2 are77%,100%,70%and 100%respectively.Conclusion:The clinical utility of the joint detection of four-gene methylation markers in the diagnosis of colorectal cancer is better than that of fecal occult blood detection,and the clinical utility of fecal samples is better than that of plasma samples.There is a significant difference in test results before and after surgery.