Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China.
1Gene Bio-tech Co., Ltd., Hangzhou, 310026, Zhejiang, China.
J Cancer Res Clin Oncol. 2019 Oct;145(10):2423-2432. doi: 10.1007/s00432-019-02992-2. Epub 2019 Aug 27.
The mortality of colorectal cancer ranked fifth in China according to cancer statistics in 2015. Cancer screening had been repeatedly proved to play a vital role in decreasing the incidence and mortality of colorectal cancer, but the existing screening methods could not meet the requirements. So it is of urgent need to develop a non-invasive, convenient and accurate screening method.
In this study, stool samples were collected from 102 colorectal cancer, 20 colorectal adenoma, 6 hyperplastic polyps patients and 105 normal controls, and stool DNA was extracted for detection of methylation (BMP3, NDRG4, SDC2 and SFRP2) and KRAS mutations. Meanwhile, hemoglobin in stool samples was detected by immunoassays. Then, the logistic regression model used for classification was built with these biomarkers, and a ROC curve was drawn to evaluate the performance of each biomarker and the panel of them. Meanwhile, conventional serum biomarkers were detected for the comparison of positive rate in colorectal cancer between serum biomarkers and stool DNA biomarkers.
As a result, a classification model built with methylation of SDC2 and SFRP2, KRAS mutations and hemoglobin showed a sensitivity of 91.4% for colorectal cancer and 60% for adenoma with the specificity of 86.1%. Compared with it, most of the conventional serum biomarkers showed a sensitivity of less than 20% for colorectal cancer which was significantly lower than stool DNA biomarkers.
A novel panel comprised of stool DNA biomarkers was of much higher sensitivity and specificity in early screening of colorectal neoplasms than conventional serum biomarkers.
根据 2015 年癌症统计数据,结直肠癌的死亡率在中国位居第五。癌症筛查已被反复证明对降低结直肠癌的发病率和死亡率起着至关重要的作用,但现有的筛查方法仍不能满足需求。因此,迫切需要开发一种非侵入性、方便和准确的筛查方法。
本研究收集了 102 例结直肠癌、20 例结直肠腺瘤、6 例增生性息肉患者和 105 例正常对照者的粪便样本,并提取粪便 DNA 进行甲基化(BMP3、NDRG4、SDC2 和 SFRP2)和 KRAS 突变检测。同时,采用免疫分析法检测粪便样本中的血红蛋白。然后,使用这些生物标志物建立用于分类的逻辑回归模型,并绘制 ROC 曲线以评估每个生物标志物和标志物组合的性能。同时,检测了常规血清生物标志物,以比较血清生物标志物和粪便 DNA 生物标志物在结直肠癌中的阳性率。
结果表明,由 SDC2 和 SFRP2 的甲基化、KRAS 突变和血红蛋白构建的分类模型对结直肠癌的敏感性为 91.4%,对腺瘤的敏感性为 60%,特异性为 86.1%。相比之下,大多数常规血清生物标志物对结直肠癌的敏感性均低于 20%,明显低于粪便 DNA 生物标志物。
由粪便 DNA 生物标志物组成的新型标志物在结直肠肿瘤的早期筛查中具有更高的敏感性和特异性,优于常规血清生物标志物。