Novel urine cell-free DNA methylation markers for hepatocellular carcinoma

Selena Y. Lin, Wei Xia, Amy K. Kim, Dion Chen, Shelby Schleyer, Lin Choi, Zhili Wang, James P. Hamilton, Harry Luu, Hie Won Hann, Ting Tsung Chang, Chi Tan Hu, Abashai Woodard, Terence P. Gade, Ying Hsiu Su

研究成果: Article同行評審

摘要

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.

原文English
文章編號21585
期刊Scientific reports
13
發行號1
DOIs
出版狀態Published - 2023 12月

All Science Journal Classification (ASJC) codes

  • 多學科

指紋

深入研究「Novel urine cell-free DNA methylation markers for hepatocellular carcinoma」主題。共同形成了獨特的指紋。

引用此