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

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

PROVIDER: PRJNA628686 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11615800_1.fastq.gz	Fastqsanger.gz
	SRR11615800_2.fastq.gz	Fastqsanger.gz
	SRR11615900_1.fastq.gz	Fastqsanger.gz
	SRR11615900_2.fastq.gz	Fastqsanger.gz
	SRR11616000_1.fastq.gz	Fastqsanger.gz

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

Project description:Owing to high cancer-specificity, DNA methylation alterations have emerged as front-runners in cell-free DNA (cf-DNA) biomarker development. However, much effort to date has focused on single cancers and have not explored the possibility of developing a pan-cancer diagnostic assay. Here, we undertook a genome-wide DNA methylation analysis for multiple gastrointestinal (GI) cancers, to develop a panGI diagnostic assay. By analyzing the DNA methylation data from 1940 tumor and adjacent normal tissues from TCGA and GSE72872 datasets, we first identified the differentially methylated regions (DMRs) between individual GI cancers and adjacent normal tissues, as well as across all GI cancers. We next prioritized a list of 67,832 tissue DMRs encompassing a 25.6 Mb genomic region by incorporating all significant DMRs across various GI cancers to design a custom SeqCap Epi, targeted bisulfite sequencing platform. Subsequent investigation of these tissue-specific DMRs in 300 cf-DNA specimens and applying machine learning algorithms led to the development of three distinct categories of DMR panels: 1) Cancer-specific biomarker panels with an AUC values of 0.98 (Colorectal cancer, CRC), 0.94 (Esophageal squamous cell carcinoma, ESCC), 0.90 (Esophageal adenocarcinoma, EAC), 0.90 (Gastric cancer, GC), 0.98 (Hepatocellular carcinoma, HCC), and 0.85 (Pancreatic ductal adenocarcinoma, PDAC); 2) A pan-GI panel that detected all GI cancers with an AUC of 0.90; and 3) A multi-cancer prediction panel, EpiPanGI Dx, with a prediction accuracy around 0.85-0.95 for most GI cancers. Utilizing a novel biomarker discovery approach, we provide first evidence for a cell-free DNA methylation biomarker assay that offer a robust diagnostic accuracy for all gastrointestinal cancers.

2021-08-27 | GSE149438 | GEO

EpiPanGI Dx: A Cell-free DNA Methylation Fingerprint for the Early Detection of Gastrointestinal Cancers.

Project description:PurposeDNA methylation alterations have emerged as front-runners in cell-free DNA (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 designHerein, we performed a genome-wide DNA methylation analysis of multiple GI cancers to develop a pan-GI diagnostic assay. By analyzing DNA methylation data from 1,781 tumor and adjacent normal tissues, we first identified differentially methylated regions (DMR) 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 cfDNA specimens and applied machine learning algorithms to develop three distinct categories of DMR panels RESULTS: We identified three distinct DMR panels: (i) 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); (ii) a pan-GI panel that detected all GI cancers with an AUC of 0.88; and (iii) a multi-cancer (tissue of origin) prediction panel, EpiPanGI Dx, with a prediction accuracy of 0.85-0.95 for most GI cancers.ConclusionsUsing a novel biomarker discovery approach, we provide the first evidence for a cfDNA methylation assay that offers robust diagnostic accuracy for GI cancers.

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