粪便多配体聚糖2基因甲基化在结直肠恶性肿瘤进展的相关性

Correlation between fecal syndecan-2 gene methylation and colorectal carcinoma progression

目的探讨粪便多配体聚糖2(SDC2)基因甲基化在结直肠恶性肿瘤(CRC)进展中的相关性。方法收集2018年4月至2019年7月上海交通大学医学院附属松江医院经结肠镜检查(和/或)病理诊断的133例受试者,其中44例CRC、61例进展期腺瘤(AA)和28例对照者(CRC和AA均为阴性者)为研究对象。每例收集两份粪便标本,采用前瞻性双盲配对法对标本分别进行一次实时定量SDC2基因甲基化特异性聚合酶链反应(qMSP)和粪便隐血免疫化学法(FIT)检测,并比较两种方法的敏感度和特异度。结合临床术后病理标本及分期,计数资料采用Fisher确切概率检验分析,计量资料使用秩和检验Kruskal-Wallis(3组之间)和Mann-Whitney法(两组之间)分析;采用Spearman相关分析CRC的SDC2甲基化Ct值与肿瘤直径、分期、浸润深度和淋巴结转移的相关性。结果在CRC组和AA组中SDC2甲基化敏感度均显著高于FIT(0.909比0.614,P<0.05和0.525比0.164,P<0.01),差异均有统计学意义;CRC组、AA组和对照组的SDC2甲基化Ct值M(P25~P75),35.02(31.32~37.87),38.90(37.26~51.00)和51.00(40.22~51.00),CRC组SDC2甲基化Ct值显著低于AA组,AA组SDC2甲基化Ct值显著低于对照组(Z=-5.213、-4.048,P<0.01),差异均有统计学意义;单变量相关分析提示,CRC组SDC2的Ct值与肿瘤直径、分期、浸润深度和淋巴结转移呈负相关(r=-0.422、-0.437、-0.371、-0.417,P<0.05),与年龄呈正相关(r=0.308,P<0.05),差异均有统计学意义。结论粪便SDC2甲基化在结直肠肿瘤检查的敏感度显著高于FIT,SDC2甲基化程度与CRC肿瘤进展程度呈正相关。

Objective To investigate the correlation between fecal syndecan-2(SDC2)gene methylation and colorectal carcinoma(CRC)progression.Methods A total of 133 subjects diagnosed by colonoscopy(and/or)pathology in Songjiang District Central Hospital from April 2018 to July 2019 were collected and divided into three groups:CRC group(n=44),advanced adenoma group(AA group)(n=61)and control group(CRC-and AA-)(n=28).With the prospective double-blind paired method,two fecal samples were collected from each case,and tested by real time quantitative methylation specific polymerase chain reaction(PCR)(qMSP)(SDC2 methylation)and fecal immunochemical test(FIT)respectively,and the sensitivity and specificity of the two methods were compared.In combination with clinical postoperative pathological specimens and staging,Fisher exact probability test was used to analyze the counting data,Rank sum test of Kruskal-wallis method(among the three groups)and Mann-Whitney method(between the two groups)were used to analyze the quantitative data,and Spearman correlation was analyzed between the Ct value of SDC2 methylation in CRC group and tumor diameter,staging,depth of infiltration and lymph node metastasis.Results The sensitivity of SDC2 methylation in CRC group and AA group was both significantly higher than that of FIT(0.909 vs.0.614,P<0.05 and 0.525 vs.0.164,P<0.01).The Ct values of SDC2 methylation in CRC group,AA group and control group were M(P25-P75):35.02(31.32-37.87),38.90(37.26-51.00)and 51.00(40.22-51.00).The Ct values of SDC2 methylation in CRC group were significantly lower than those in AA group,while those in AA group were significantly lower than those in control group(Z=-5.213,-4.048,P<0.01).Univariate correlation analysis showed that the Ct value of SDC2 methylation in CRC group was negatively correlated with tumor diameter,staging,invasion depth and lymph node metastasis(r=-0.422,-0.437,-0.371,-0.417,P<0.05),and positively correlated with age(r=0.308,P<0.05).Conclusion The sensitivity of fecal SDC2 methylation in CRC and AA examination is significantly higher than that of FIT,and the degree of SDC2 methylation is positively correlated with the degree of CRC tumor progression.