Discovery and Validation of a Novel Dual-Targets Blood Test for Detection of Hepatocellular Carcinoma from Cirrhosis

In tissue discovery cohort, we utilized human methylome bisulfite panel which targets 123 Mb of genomic content to identify DNA methylation-based biomarkers starting with 43 primary HCC tissue and 32 adjacent normal tissue samples. 21 candidate markers were validated in 55 HCC, 55 cirrhosis and 50 healthy plasma samples by bisulfite sequencing in plasma discovery cohort. Technically validated methylated candidates were then biologically validated on 50 primary HCC tissue and 50 adjacent normal tissue samples(partial samples as performed in tissue discovery) using quantitive methylation-specific PCR(MS-qPCR), yielding six candidate DNA markers for further validation. In phase 1 plasma cohort, candidate markers were validated in 53 HCC, 52 cirrhosis, 20 benign liver diseases and 50 healthy plasma samples. Qliver model consists of OSR2 and TSPYL5 were selected as the most informative markers which could be applied to validate clinical feasibility of best performing markers in a larger case-control study. Finally, Qliver model was further validated in 67 HCC and 81 cirrhosis plasma samples in phase 2 plasma cohort. In this repository, we publicly release the raw data of 43 primary HCC tissues and 32 adjacent normal tissue samples.