Long Lu, Sun Qian, Yang Fang, Zhou Hui, Wang Yu, Xiao Changhe, He Qing, Yi Bin
Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, China.
Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, China.
Clin Biochem. 2024 Feb;124:110717. doi: 10.1016/j.clinbiochem.2024.110717. Epub 2024 Jan 13.
Recent studies have identified methylated SDC2 and NDRG4 in colorectal cancer (CRC), however, the diagnostic value of the combined two genes remains undefined. This study aims to investigate the methylation of SDC2 and NDRG4 in stool samples and their application in diagnosis of CRC.
Five groups were enrolled in our study which consisted of CRC (n = 138), advanced adenomas (n = 27), polyp (n = 35), intestinal disease control (n = 150), and healthy individuals (n = 28). Methylation status of SDC2 and NDRG4 in fecal samples were tested with appropriate commercial kits. Primary data were collected and statistical analyses were performed.
The positive rates of both SDC2 and NDRG4 methylation in stool samples of CRC group were significantly higher (P < 0.001) than those of either group of advanced adenomas, or polyp, or intestinal disease or the healthy control. It was suggested that both methylated SDC2,NDRG4, SDC2/NDRG4 and age were independent risk factors for CRC. The sensitivity of SDC2 and NDRG4 for CRC diagnosis were 73.9 % and 63.0 %, respectively, while SDC2 combined with NDRG4 had a higher sensitivity of 85.5 %. The specificity of SDC2, NDRG4 and SDC2 combined with NDRG4 achieved 91.6 %, 88.3 % and 84.6 %, respectively. The AUC for methylated SDC2 and NDRG4 were 0.828 (95 % CI: 0.780-0.876) and 0.757 (95 % CI: 0.703-0.811), respectively. In contrast, SDC2 combined with NDRG4 improved the AUC to 0.850 (95 % CI: 0.807-0.893).
This research confirmed the significance of detection of SDC2 and NDRG4 methylation by using noninvasive samples of stool. More importantly, attributing to their high level and frequency of methylation in stool, SDC2 and NDRG4 could be promising biomarkers for stool-based method for screening and early diagnosis of CRC, especially when combined.
近期研究已在结直肠癌（CRC）中鉴定出甲基化的SDC2和NDRG4，然而，这两个基因联合检测的诊断价值仍不明确。本研究旨在探讨粪便样本中SDC2和NDRG4的甲基化情况及其在CRC诊断中的应用。
本研究纳入五组人群，包括CRC患者（n = 138）、进展期腺瘤患者（n = 27）、息肉患者（n = 35）、肠道疾病对照组（n = 150）和健康个体（n = 28）。使用合适的商业试剂盒检测粪便样本中SDC2和NDRG4的甲基化状态。收集原始数据并进行统计分析。
CRC组粪便样本中SDC2和NDRG4甲基化的阳性率均显著高于进展期腺瘤组、息肉组、肠道疾病组或健康对照组（P < 0.001）。提示甲基化的SDC2、NDRG4、SDC2/NDRG4以及年龄均是CRC的独立危险因素。SDC2和NDRG4对CRC诊断的敏感度分别为73.9%和63.0%，而SDC2与NDRG4联合检测的敏感度更高，为85.5%。SDC2、NDRG4以及SDC2与NDRG4联合检测的特异度分别达到91.6%、88.3%和84.6%。甲基化SDC2和NDRG4的曲线下面积（AUC）分别为0.828（95%CI：0.780 - 0.876）和0.757（95%CI：0.703 - 0.811）。相比之下，SDC2与NDRG4联合检测可将AUC提高至0.850（95%CI：0.807 - 0.893）。
本研究证实了通过无创粪便样本检测SDC2和NDRG4甲基化的意义。更重要的是，由于SDC2和NDRG4在粪便中的甲基化水平和频率较高，它们有望成为基于粪便的CRC筛查和早期诊断方法的生物标志物，尤其是联合检测时。
