EpiPanGI Dx:胃肠道肿瘤早期检测的新工具
创作:章台柳 审核:章台柳 09月06日
  • 收集多种胃肠道肿瘤(GI,1781个)及癌旁组织进行全基因组DNA甲基化分析;
  • 鉴定出单种癌症的差异性甲基化区域(DMRs),区分癌症和癌旁的预测效率为:结直肠癌、肝细胞癌、食管鳞状细胞癌、胃癌、食管腺癌和胰腺导管腺癌的AUC分别为0.98、0.98、0.94、0.90、0.90和0.85;
  • 区分所有GI肿瘤和癌旁的DMRs,AUC为0.88;
  • 分析组织特异性DMR并在300个无细胞DNA样本中进行验证,设计出预测多癌(起源组织)的EpiPanGI Dx,准确率达0.85-0.95.
Clinical Cancer Research近期发表的文章,通过对胃肠道癌(GI)肿瘤组织和癌旁组织进行DNA甲基化分析,鉴定出差异性甲基化区域,使用机器学习设计出用于区分单种胃肠道癌症、泛-胃肠道癌症、多种胃肠道癌症的预测特征,同时使用无细胞DNA样本进行验证。即研究首次揭示游离DNA甲基化分析用于诊断GI肿瘤具有准确性。

EpiPanGI Dx: A cell-free DNA methylation fingerprint for the early detection of gastrointestinal cancers

EpiPanGI Dx:用于胃肠道肿瘤早期检测的无细胞DNA甲基化指纹图谱


08-31, Article

Abstract & Authors:展开

Purpose DNA methylation alterations have emerged as front-runners in cfDNA biomarker development. However, much effort to date has focused on single cancers. In this context, gastrointestinal (GI) cancers constitute the second leading cause of cancer-related deaths worldwide; yet there is no blood-based assay for the early detection and population screening of GI cancers. Experimental Design Herein, we performed a genome-wide DNA methylation analysis of multiple gastrointestinal (GI) cancers to develop a pan-GI diagnostic assay. By analyzing DNA methylation data from 1781 tumor and adjacent normal tissues, we first identified differentially methylated regions (DMRs) between individual GI cancers and adjacent normal, as well as across GI cancers. We next prioritized a list of 67,832 tissue DMRs by incorporating all significant DMRs across various GI cancers to design a custom, targeted bisulfite-sequencing platform. We subsequently validated these tissue-specific DMRs in 300 cell-free DNA-specimens and applied machine learning algorithms to develop three distinct categories of DMR-panels. Results We identified three distinct DMR panels. 1) Cancer-specific biomarker panels with AUC values of 0.98 (colorectal cancer), 0.98 (hepatocellular carcinoma), 0.94 (esophageal squamous cell carcinoma), 0.90 (gastric cancer), 0.90 (esophageal adenocarcinoma), and 0.85 (pancreatic ductal adenocarcinoma); 2) A pan-GI panel that detected all GI cancers with an AUC of 0.88; and 3) A multi-cancer (tissue of origin) prediction panel, EpiPanGI Dx, with a prediction accuracy of 0.85 - 0.95 for most GI cancers. Conclusions Using a novel biomarker discovery approach, we provide first evidence for a cfDNA methylation assay that offers robust diagnostic accuracy for GI cancers.

First Authors:
Raju Kandimalla,Jianfeng Xu

Correspondence Authors:
Wei Li,Ajay Goel

All Authors:
Raju Kandimalla,Jianfeng Xu,Alexander Link,Takatoshi Matsuyama,Kensuke Yamamura,M Iqbal Parker,Hiroyuki Uetake,Francesc Balaguer,Erkut Borazanci,Susan Tsai,Douglas Evans,Stephen J Meltzer,Hideo Baba,Randall Brand,Daniel Von Hoff,Wei Li,Ajay Goel