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- Title
Novel urine cell-free DNA methylation markers for hepatocellular carcinoma.
- Authors
Lin, Selena Y.; Xia, Wei; Kim, Amy K.; Chen, Dion; Schleyer, Shelby; Choi, Lin; Wang, Zhili; Hamilton, James P.; Luu, Harry; Hann, Hie-Won; Chang, Ting-Tsung; Hu, Chi-Tan; Woodard, Abashai; Gade, Terence P.; Su, Ying-Hsiu
- 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.
- Subjects
CELL-free DNA; DNA methylation; HEPATOCELLULAR carcinoma; NUCLEOTIDE sequencing; URINE
- Publication
Scientific Reports, 2023, Vol 13, Issue 1, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-023-48500-y