联合检测粪便ECAD基因甲基化和隐血在结直肠癌诊断中的价值

目的 探讨粪便ECAD甲基化联合隐血在结直肠癌(CRC)中的诊断价值.方法 收集50例健康体检者、50例结直肠良性病变者、50例CRC患者的粪便标本.利用甲基化特异性PCR(MSP)的方法 检测粪便中ECAD基因的甲基化情况,根据肠镜病理诊断进行验证,比较粪便ECAD甲基化率、粪便潜血实验(FOBT)及两者联合对CRC诊断的敏感性及特异性,并进行统计学分析.结果 CRC患者粪便ECAD甲基化率(78%)明显高于健康体检者(16%)和结直肠良性病变者(26%);同时,CRC患者FOBT阳性率(64%)亦明显高于健康体检者(2%)和结直肠良性病变者(26%),差异有统计学意义(P<0.001).粪便ECAD甲基化率与CRC患者肿瘤数目(P=0.048)、病理分级(P=0.006)、TNM分级(P=0.002)及淋巴结转移(P=0.002)密切相关.CRC患者粪便FOBT敏感度为64%(95%CI:49.1%~76.7%),特异度为86%(95%CI:77.3%~91.9%);而ECAD敏感度为78%(95%CI:63.7%~88.0%),特异度为79%(95%CI:69.5%~86.2%).ROC曲线分析提示ECAD的ROC曲线下面积(AUC)为0.795(95%CI为0.716~0.874),略高于FOBT的AUC(0.750,95%CI:0.661~0.839),而两种联合的AUC为0.806(95%CI:0.728~0.884),诊断效能最高.结论 粪便ECAD基因甲基化的检测是早期诊断CRC的有效方法 ,其联合FOBT能有效提高诊断效能.

The significance of detection of ECAD gene methylation in combination with FOBT in stool in the diagnosis of colorectal cancer

Objective To investigate the diagnostic value of detecting methylation level of ECAD in combination with fecal occult blood test (FOBT) in stool for colorectal cancer (CRC).Methods A total of 50 healthy people, 50 patients with colorectal benign lesion and 50 CRC patients were included in this study .The stool samples from these pa-tients were collected and ECAD gene methylation level was detected using methylation specific PCR ( MSP) .The clinical status and the pathological diagnosis of all patients were confirmed by colonoscopy .The sensitivity and specificity of ECAD and FOBT for the diagnosis of CRC were analyzed using statistic method .Results The positive rate of stool ECAD gene methylation in CRC patients was 78%, which was significantly higher than control groups (21%).Consistently, the posi-tive rate of FOBT in CRC patients was also significantly higher than control groups (64% vs.14%).Besides, ECAD methylation level in stool was significantly associated with tumor number ( P=0.048 ) , histological type ( P=0.006 ) , TNM stage (P=0.002), and lymph node metastasis (P=0.002).The sensitivity and specificity of stool FOBT methyla-tion for CRC diagnosis were 64%(95%CI:49.1-76.7%) and 86%(95%CI:77.3-91.9%), respectively.Where-as the sensitivity and specificity of ECAD were 78%(95%CI:63.7-88.0%) and 79%(95%CI:69.5-86.2%), re-spectively.The under-ROC curve area of ECAD was 0.795 (95%CI:0.716-0.874%), which was higher than that of FOBT (AUCROC:0.806, 95%CI:0.728-0.884%).More importantly, the area of combined detection of two factors reached 0.806 (95%CI:0.728-0.884%).Conclusion ECAD gene methylation in stool is an efficient method for ear-ly diagnosis for CRC patients .The combined detection of ECAD and FOBT in stool may increase the accuracy of diagnosis of CRC.