大肠肿瘤Syndecan-2基因甲基化及临床意义

目的探讨Syndecan-2(SDC2)基因甲基化对大肠肿瘤的诊断价值并分析其与临床病理特征和预后的关系。方法收集2014年1月至2016年12月大肠癌及配对癌旁石蜡组织各54例以及大肠腺瘤石蜡组织30例,另收集2018年8月至2019年5月大肠癌患者粪便32例、大肠腺瘤患者粪便28例及正常人群粪便40例。通过定量甲基化特异性PCR(QMSP)检测各样本中SDC2基因启动子区甲基化的发生率,分析SDC2基因甲基化检出率与临床病理特征的关系,并比较不同SDC2甲基化水平大肠癌患者的总生存期(OS)。结果SDC2基因甲基化在大肠癌、大肠腺瘤和癌旁组织中的阳性率分别为85.2%(46/54)、66.7%(20/30)和5.6%(3/54),在大肠癌患者、大肠腺瘤患者和正常人群粪便中的阳性率分别为78.1%(25/32)、57.1%(16/28)和2.5%(1/40)。与癌旁组织比较,SDC2甲基化在大肠癌组织和大肠腺瘤组织中均更易被检测到(P=0.000,P=0.000);SDC2甲基化阳性率在大肠癌患者粪便和大肠腺瘤患者粪便中明显高于正常人群粪便(P=0.000,P=0.000)。对于组织或粪便样本,大肠癌与大肠腺瘤SDC2甲基化阳性率的差异无统计学意义(P>0.05)。对于组织和粪便样本,SDC2基因甲基化与大肠癌和大肠腺瘤临床病理特征均无关(P>0.05)。与正常粪便比较,SDC2基因甲基化筛查大肠癌和大肠腺瘤的灵敏度分别为78.1%和57.1%,特异度均为97.5%。大肠癌组织SDC2基因甲基化低水平组的中位OS为68.0个月,与高水平组的70.0个月比较,差异无统计学意义(P=0.752)。结论SDC2基因甲基化是筛查大肠癌的有效分子标志物,但对大肠癌的预后无明显指导意义。

Syndecan-2 gene methylation in colorectal neoplasms and its clinical significance

Objective To evaluate the diagnostic value and prognostic significance of syndecan 2(SDC2)gene methylation and its relationship with clinicopathological features and prognosis in colorectal neoplasms.Methods The samples of colorectal cancer(n=54)and paired normal tissues(n=54),and colorectal adenoma paraffin tissues(n=30)were collected from January 2014 to December 2016.The stools from colorectal cancer patients(n=32),colorectal adenoma patients(n=28)and normal controls(n=40)were collected from August 2018 to May 2019.The incidence of SDC2 gene promoter methylation was detected by quantitative methylated specific PCR(QMSP).The relationship between the positive rate of SDC2 methylation and clinicopathological features in colorectal neoplasms,and the prognosis of different SDC2 gene methylation levels in colorectal cancer patients were analyzed.Results The positive rates of SDC2 methylation were 85.2%(46/54),66.7%(20/30)and 5.6%(3/54)in colorectal cancer tissues,colorectal adenoma tissues and paired normal tissues,and 78.1%(25/32),57.1%(16/28)and 2.5%(1/40)in stools from colorectal cancer patients,colorectal adenoma patients and normal controls,respectively.Compared with paired normal tissues,SDC2 methylation was more easily detected in colorectal cancer and colorectal adenoma tissues(P=0.000,P=0.000);compared with normal control stools,the positive rate of SDC2 gene methylation was higher in stools of patients with colorectal cancer and colorectal adenoma(P=0.000,P=0.000).However,there was no significant difference between colorectal cancer and colorectal adenoma in both tissue samples and stool samples(P>0.05).For samples from different sources,SDC2 gene methylation was not associated with the clinicopathological features of colorectal neoplasms(P>0.05).The sensitivity of SDC2 gene methylation to colorectal cancer and adenoma in stools was 78.1%and 57.1%,respectively,and the specificity was both 97.5%.The median overall survival of low-level group of SDC2 gene methylation was 68.0 months and that of high-level group was 70.0 months,the difference was not statistically significant(P=0.752).Conclusion SDC2 methylation is an effective molecular marker for screening colorectal cancer,but it has no obvious guiding effect on the prognosis of colorectal cancer.