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| Status |
Public on Aug 22, 2014 |
| Title |
Expression profiles of 186-gene signature in U.S. hepatitis C virus (HCV)-related liver cirrhosis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
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.
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| Contributor(s) |
King L, Canasto-Chibuque C, Johnson K, Yip S, Chen X, Kojima K, Deshmukh M, Venkatesh A, Tan PS, Villanueva A, Sangiovanni A, Nair V, Mahajan M, Kobayashi M, Kumada H, Iavarone M, Colombo M, Friedman SL, Llovet JM, Chung RT, Hoshida Y |
| Citation(s) |
25143343, 25506552 |
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| Submission date |
Jan 15, 2014 |
| Last update date |
Jul 31, 2019 |
| Contact name |
Yujin Hoshida |
| Organization name |
University of Texas Southwestern Medical Center
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| Street address |
5323 Harry Hines Blvd
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| City |
Dallas |
| State/province |
TX |
| ZIP/Postal code |
75390 |
| Country |
USA |
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| Platforms (1) |
| GPL17230 |
NanoString Prognostic Liver Signature (PLS) panel (186 genes, ver.0) |
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| Samples (145)
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| This SubSeries is part of SuperSeries: |
| GSE54102 |
A genomic and clinical prognostic index for hepatitis C-related early-stage cirrhosis that predicts clinical deterioration |
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| Relations |
| BioProject |
PRJNA235187 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE54100_raw.txt.gz |
74.5 Kb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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