EpiPanGI Dx: A Cell-free DNA Methylation fingerprint for the early detection of Gastrointestinal cancers

Kandimalla R, Xu J, Link A, Matsuyama T, Yamamura K, Parker MI, Uetake H, Balaguer F, Borazanci E, Tsai S, Evans D, Meltzer SJ, Baba H, Brand R, Von Hoff D, Li W, Goel A (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Clinical Cancer Research American Association for Cancer Research

Book Volume: 27

Pages Range: 6135-6144

Journal Issue: 22

DOI: 10.1158/1078-0432.CCR-21-1982

Abstract

Purpose: DNA methylation alterations have emerged as frontrunners 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 bloodbased assay for the early detection and population screening of GI cancers. Experimental Design: Herein, 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) cancerspecific 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. Conclusions: Using a novel biomarker discovery approach, we provide the first evidence for a cfDNA methylation assay that offers robust diagnostic accuracy for GI cancers.

Authors with CRIS profile

Alexander Link

Involved external institutions

Medical College of Wisconsin (MCW) US United States (USA) (US) Institute of Science Tokyo (ISCT) / 東京科学大学 JP Japan (JP) Otto-von-Guericke-Universität Magdeburg DE Germany (DE) Universitat de Barcelona (UB) / University of Barcelona ES Spain (ES) University of Pittsburgh US United States (USA) (US) Johns Hopkins Hospital US United States (USA) (US) Baylor College of Medicine US United States (USA) (US) HonorHealth US United States (USA) (US) Kumamoto University / 熊本大学 JP Japan (JP) Baylor Scott & White Health US United States (USA) (US) University of Cape Town (UCT) ZA South Africa (ZA)

How to cite

APA:

Kandimalla, R., Xu, J., Link, A., Matsuyama, T., Yamamura, K., Parker, M.I.,... Goel, A. (2021). EpiPanGI Dx: A Cell-free DNA Methylation fingerprint for the early detection of Gastrointestinal cancers. Clinical Cancer Research, 27(22), 6135-6144. https://doi.org/10.1158/1078-0432.CCR-21-1982

MLA:

Kandimalla, Raju, et al. "EpiPanGI Dx: A Cell-free DNA Methylation fingerprint for the early detection of Gastrointestinal cancers." Clinical Cancer Research 27.22 (2021): 6135-6144.

BibTeX: Download