A sensitive and robust plasma-based DNA methylation panel for early detection of target gastrointestinal cancers,Neoplasia

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A sensitive and robust plasma-based DNA methylation panel for early detection of target gastrointestinal cancers
Neoplasia ( IF 4.8 ) Pub Date : 2023-11-01 , DOI: 10.1016/j.neo.2023.100941
Yanmiao Dai ₁ , Hui Li ₂ , Qianqian Wu ₃ , Jie Wang ₁ , Kai Wang ₄ , Sujuan Fei ₅ , Bing Pei ₆ , Lishuang Song ₄ , Guangxia Chen ₃ , Yong Ma ₇ , Chenjing Xia ₁ , Shangmin Xiong ₈ , Minxue Zheng ₇ , Ying Xue ₉ , Guodong Zhao ₈ , Hongwei Xu ₁

Affiliation

Department of Spleen and Stomach Diseases, Kunshan Hospital of traditional Chinese Medicine, Kunshan Jiangsu 215300, China.
Department of Gastroenterology, The First People's Hospital of Xuzhou, Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou Jiangsu 221002, China; Department of Gastroenterology, Affiliated Hospital of Xuzhou Medical University, Xuzhou Jiangsu 221002, China.
Department of Gastroenterology, The First People's Hospital of Xuzhou, Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou Jiangsu 221002, China.
Suzhou VersaBio Technologies Co. Ltd., Kunshan Jiangsu 215300, China.
Department of Gastroenterology, Affiliated Hospital of Xuzhou Medical University, Xuzhou Jiangsu 221002, China.
Department of Clinical Laboratory, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian, Jiangsu, 223800, China.
Zhejiang University Kunshan Biotechnology Laboratory, Zhejiang University Kunshan Innovation Institute, Kunshan Jiangsu 215300, China; Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou Jiangsu 215163, China.
Zhejiang University Kunshan Biotechnology Laboratory, Zhejiang University Kunshan Innovation Institute, Kunshan Jiangsu 215300, China; Suzhou VersaBio Technologies Co. Ltd., Kunshan Jiangsu 215300, China.
The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou Jiangsu 215000, China.

Background

Target gastrointestinal cancers (GICs), encompassing esophageal cancer (EC), gastric cancer (GC), and colorectal cancer (CRC), originate within a single readily accessible luminal organ system and are diagnosable using endoscopy. However, endoscopy is an invasive procedure with low compliance and no plasma-based DNA methylation assay for the early detection of GICs.

Methods

Nine potential DNA methylation markers were identified and evaluated in tissue (n=60) and plasma (n=155) cohorts to select the most suitable markers. A training cohort (n=244) and a validation cohort (n=199), including GICs patients, benign tumors, gastrointestinal polyps, and controls, were enrolled to develop and validate a DNA methylation panel. An independent prospective cohort (n=158) was used to validate the panel's performance and compare it with blood protein tumor markers.

Results

Six out of nine candidate methylation markers with excellent discrimination abilities in both tissue and plasma cohorts were selected for the DNA methylation panel. The panel demonstrated high AUC values of 0.937 (EC), 0.968 (GC), and 0.987 (CRC) in training cohort, and achieved AUC values of 0.921 (EC), 0.921 (GC), and 0.959 (CRC) in validation cohort. Notably, it achieved impressive AUC values of 0.971 and 0.843 for identifying stage I GICs in the training and validation cohorts, respectively. In the prospective cohort, the six-marker panel showed comparable AUC values to CEA, AFP, and CA19-9 (0.935, 0.769, 0.663, and 0.668, respectively).

Conclusion

This study successfully developed and validated a novel, robust, sensitive, and specific plasma-based DNA methylation panel, offering a promising strategy for the early detection of GICs.

中文翻译：

灵敏且强大的基于血浆的 DNA 甲基化试剂盒，用于早期检测目标胃肠癌

背景

目标胃肠癌 (GIC)，包括食管癌 (EC)、胃癌 (GC) 和结直肠癌 (CRC)，起源于单个易于接近的管腔器官系统，可使用内窥镜检查进行诊断。然而，内窥镜检查是一种侵入性检查，依从性低，并且没有基于血浆的 DNA 甲基化检测来早期检测 GIC。

方法

在组织 (n=60) 和血浆 (n=155) 队列中鉴定和评估了九种潜在的 DNA 甲基化标记，以选择最合适的标记。招募了一个训练队列 (n=244) 和一个验证队列 (n=199)，包括 GIC 患者、良性肿瘤、胃肠道息肉和对照，以开发和验证 DNA 甲基化组。一个独立的前瞻性队列（n = 158）用于验证该小组的性能并将其与血液蛋白肿瘤标志物进行比较。

结果

9 个候选甲基化标记物中的 6 个在组织和血浆队列中都具有出色的辨别能力，被选择用于 DNA 甲基化组。该小组在训练队列中表现出 0.937 (EC)、0.968 (GC) 和 0.987 (CRC) 的高 AUC 值，并在验证队列中实现了 0.921 (EC)、0.921 (GC) 和 0.959 (CRC) 的 AUC 值。值得注意的是，在识别训练和验证队列中的 I 期 GIC 方面，它分别取得了令人印象深刻的 AUC 值 0.971 和 0.843。在前瞻性队列中，六标记物组显示出与 CEA、AFP 和 CA19-9 相当的 AUC 值（分别为 0.935、0.769、0.663 和 0.668）。