Early colorectal cancer diagnosis: A novel methylated stool DNA model enhanced the diagnostic efficiency.

IF 5.8 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY United European Gastroenterology Journal Pub Date : 2024-11-02 DOI:10.1002/ueg2.12696
Peng Yun, Kamila Kulaixijiang, Jiang Pan, Luping Yang, Nengzhuang Wang, Zheng Xu, Yaodong Zhang, Haifang Cai, Zi-Ye Zhao, Min Zhu, Hongli Yan
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Abstract

Background: Methylated stool DNA (sDNA) is a reliable noninvasive biomarker for early colorectal cancer (CRC) diagnosis. However, there are barely any diagnostic panels that can achieve both a sensitivity and specificity exceeding 90% simultaneously.

Objective: We aimed to identify a novel methylated sDNA panel and model for the early diagnosis of CRC.

Methods: We conducted methyl-CpG binding domain isolated genome sequencing (MiGS) on CpG island methylation phenotype (CIMP)-positive (n = 3) and CIMP-negative CRC tissues (n = 3) and their corresponding normal adjacent tissues. Subsequently, by utilizing both the aforementioned data and public datasets, we identified a set of promising methylated sDNA markers for CRC. Next, we validated 5 of these genes using pyrosequencing in CRC patients (n = 31). Then, we developed a combined diagnostic model (CDM) for CRC based on the methylation status of PRDM12, FOXE1, and SDC2 by a Training cohort (n = 231). Finally, the performance of CDM was evaluated in an independent multicenter Validation cohort (n = 800).

Results: A total of 1062 participants were included in this study. The area under the curve (AUC) of the CDM was 0.979 (95% CI: 0.960-0.997), and the optimal sensitivity and specificity were 97.35% and 99.05%, respectively, in the training cohort (n = 231). In the independent validation cohort (n = 800), the AUC was 0.950 (95% CI: 0.927-0.973), along with the optimal sensitivity of 92.75% and specificity of 97.21%. When CRC and advanced adenoma (AAD) were used as diagnostic targets, the model AUC was 0.945 (95% CI: 0.922-0.969), with an optimal sensitivity of 91.89% and a specificity of 95.21%. The model sensitivity for nonadvanced adenoma patients was 68.66%.

Conclusion: The sDNA diagnostic model CDM, developed from both CIMP-P and CIMP-N, exhibited exceptional performance in CRC and could serve as a potential alternative strategy for CRC screening.

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早期大肠癌诊断:新型甲基化粪便 DNA 模型提高了诊断效率。
背景:甲基化粪便 DNA(sDNA)是早期诊断结直肠癌(CRC)的一种可靠的非侵入性生物标志物。然而,几乎没有任何诊断样本能同时达到超过 90% 的灵敏度和特异性:我们的目的是为早期诊断 CRC 找出一种新型甲基化 sDNA 面板和模型:我们对CpG岛甲基化表型(CIMP)阳性(n = 3)和CIMP阴性(n = 3)的CRC组织及其相应的正常邻近组织进行了甲基-CpG结合域分离基因组测序(MiGS)。随后,通过利用上述数据和公共数据集,我们确定了一组有希望的 CRC 甲基化 sDNA 标记。接下来,我们利用热测序技术在 CRC 患者(31 人)中验证了其中的 5 个基因。然后,我们根据 PRDM12、FOXE1 和 SDC2 的甲基化状态,通过训练队列(n = 231)建立了一个 CRC 联合诊断模型(CDM)。最后,在一个独立的多中心验证队列(n = 800)中对 CDM 的性能进行了评估:本研究共纳入 1062 名参与者。CDM 的曲线下面积(AUC)为 0.979(95% CI:0.960-0.997),最佳灵敏度和特异性分别为 97.35% 和 99.05%。在独立验证队列(n = 800)中,AUC 为 0.950(95% CI:0.927-0.973),最佳灵敏度为 92.75%,特异度为 97.21%。当将 CRC 和晚期腺瘤(AAD)作为诊断目标时,模型的 AUC 为 0.945(95% CI:0.922-0.969),最佳灵敏度为 91.89%,特异性为 95.21%。非晚期腺瘤患者的模型灵敏度为 68.66%:由 CIMP-P 和 CIMP-N 发展而来的 sDNA 诊断模型 CDM 在 CRC 中表现出卓越的性能,可作为 CRC 筛查的潜在替代策略。
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来源期刊
United European Gastroenterology Journal
United European Gastroenterology Journal GASTROENTEROLOGY & HEPATOLOGY-
CiteScore
10.50
自引率
13.30%
发文量
147
期刊介绍: United European Gastroenterology Journal (UEG Journal) is the official Journal of the United European Gastroenterology (UEG), a professional non-profit organisation combining all the leading European societies concerned with digestive disease. UEG’s member societies represent over 22,000 specialists working across medicine, surgery, paediatrics, GI oncology and endoscopy, which makes UEG a unique platform for collaboration and the exchange of knowledge.
期刊最新文献
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