Journal article
Novel urine cell-free DNA methylation markers for hepatocellular carcinoma
Scientific reports, v 13(1), pp 21585-21585
07 Dec 2023
PMID: 38062093
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
An optimized hepatocellular carcinoma (HCC)-targeted methylation next generation sequencing assay was developed to discover HCC-associated methylation markers directly from urine for HCC screening. Urine cell-free DNA (ucfDNA) isolated from a discovery cohort of 31 non-HCC and 30 HCC was used for biomarker discovery, identifying 29 genes with differentially methylated regions (DMRs). Methylation-specific qPCR (MSqPCR) assays were developed to verify the selected DMRs corresponding to 8 genes (GRASP, CCND2, HOXA9, BMP4, VIM, EMX1, SFRP1, and ECE). Using archived ucfDNA, methylation of GRASP, HOXA9, BMP4, and ECE1, were found to be significantly different (p < 0.05) between HCC and non-HCC patients. The four markers together with previously reported GSTP1 and RASSF1A markers were assessed as a 6-marker panel in an independent training cohort of 87 non-HCC and 78 HCC using logistic regression modeling. AUROC of 0.908 (95% CI, 0.8656-0.9252) was identified for the 6-marker panel with AFP, which was significantly higher than AFP-alone (AUROC 0.841 (95% CI, 0.778-0.904), p = 0.0026). Applying backward selection method, a 4-marker panel was found to exhibit similar performance to the 6-marker panel with AFP having 80% sensitivity compared to 29.5% by AFP-alone at a specificity of 85%. This study supports the potential use of methylated transrenal ucfDNA for HCC screening.
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Details
- Title
- Novel urine cell-free DNA methylation markers for hepatocellular carcinoma
- Creators
- Selena Y Lin - JBS Science (United States)Wei Xia - JBS Science (United States)Amy K Kim - Johns Hopkins MedicineDion Chen - JBS Science (United States)Shelby Schleyer - JBS Science (United States)Lin Choi - JBS Science (United States)Zhili Wang - JBS Science (United States)James P Hamilton - Johns Hopkins MedicineHarry Luu - Johns Hopkins MedicineHie-Won Hann - Thomas Jefferson University HospitalTing-Tsung Chang - National Cheng Kung University HospitalChi-Tan Hu - Tzu Chi FoundationAbashai Woodard - University of PennsylvaniaTerence P Gade - University of PennsylvaniaYing-Hsiu Su - Baruch S. Blumberg Institute
- Publication Details
- Scientific reports, v 13(1), pp 21585-21585
- Publisher
- Springer Nature
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:001142614900047
- Scopus ID
- 2-s2.0-85178887779
- Other Identifier
- 991021811643004721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Oncology