Dataset Information

High-throughput single-cell RNA-Seq profiling of DMSO-differentiated Huh7.5.1 undergoing or not long-term HCV infection

ABSTRACT: Hepatocellular carcinoma (HCC) is the second leading cause of cancer death worldwide, indicating urgent need for novel preventive strategies. Cancer chemoprevention discovery has been challenging due to the absence of tractable and clinically relevant model systems. Here, we developed a simple and robust human liver cell-based system, in which persistent hepatitis C virus (HCV) infection induces a HCC risk signature robustly predicting long-term HCC risk in cirrhotic patients. Using single-cell RNA-Seq analysis we observed a virus-dependent induction of the HCC high-risk gene signature and EGFR/MAPK signaling in HCV-infected liver cells. Our system, modeling the cell circuits encoded in the clinical HCC risk signature, enables investigation of the mechanisms of hepatocarcinogenesis and the discovery of cancer preventive strategies for HCC.

ORGANISM(S): Hepacivirus hominis Homo sapiens

PROVIDER: GSE81040 | GEO | 2021/07/01

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:OBJECTIVE: The number of patients with HCV-related cirrhosis is increasing, leading to a rising risk of complications and death. Prognostic stratification in patients with early-stage cirrhosis is still challenging. We aimed to develop and validate a clinically useful prognostic index based on genomic and clinical variables to identify patients at high risk of disease progression. DESIGN: We developed a prognostic index, comprised of a 186-gene signature validated in our previous genome-wide profiling study, bilirubin (>1?mg/dL) and platelet count (<100?000/mm3), in an Italian HCV cirrhosis cohort (training cohort, n=216, median follow-up 10?years). The gene signature test was implemented using a digital transcript counting (nCounter) assay specifically developed for clinical use and the prognostic index was evaluated using archived specimens from an independent cohort of HCV-related cirrhosis in the USA (validation cohort, n=145, median follow-up 8?years). RESULTS: In the training cohort, the prognostic index was associated with hepatic decompensation (HR=2.71, p=0.003), overall death (HR=6.00, p<0.001), hepatocellular carcinoma (HR=3.31, p=0.001) and progression of Child-Turcotte-Pugh class (HR=6.70, p<0.001). The patients in the validation cohort were stratified into high-risk (16%), intermediate-risk (42%) or low-risk (42%) groups by the prognostic index. The high-risk group had a significantly increased risk of hepatic decompensation (HR=7.36, p<0.001), overall death (HR=3.57, p=0.002), liver-related death (HR=6.49, p<0.001) and all liver-related adverse events (HR=4.98, p<0.001). CONCLUSIONS: A genomic and clinical prognostic index readily available for clinical use was successfully validated, warranting further clinical evaluation for prognostic prediction and clinical trial stratification and enrichment for preventive interventions. 145 liver tissue needle biopsy specimens from U.S. HCV cirrhosis cohort patients with histologically proven cirrhosis lacking evidence and a history of hepatic decompensation or HCC.

Dataset Information

High-throughput single-cell RNA-Seq profiling of DMSO-differentiated Huh7.5.1 undergoing or not long-term HCV infection

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets