Details

Autor(en) / Beteiligte

• 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

Titel

Novel urine cell-free DNA methylation markers for hepatocellular carcinoma

Ist Teil von

• Scientific reports, 2023-12, Vol.13 (1), p.21585-21585, Article 21585

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.