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E-GEOD-54101 - Gene-expression profiles of paired biopsies and explanted liver from hepatitis C virus (HCV)-infected individuals

Status
Released on 22 August 2014, last updated on 1 September 2014
Organism
Homo sapiens
Samples (9)
Array (1)
Protocols (7)
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. Paired core needle liver biopsy specimens obtained with time interval ranging from 1 month to 7.5 years from three individuals, and liver tissues from right and left lobes of explanted liver with chronic HCV infection from one individual.
Experiment type
transcription profiling by array 
Contacts
Angelo Sangiovanni, Anu Venkatesh, Augusto Villanueva, Claudia Canasto-Chibuque, Hiromitsu Kumada, Josep M Llovet, Kara Johnson, Kensuke Kojima, Lindsay King, Manjeet Deshmukh, Masahiro Kobayashi, Massimo Colombo, Massimo Iavarone, Milind Mahajan, Poh S Tan, Raymond T Chung, Scott L Friedman, Shun Yip, Venugopalan Nair, Xintong Chen, Yujin Hoshida
Citation
A genomic and clinical prognostic index for hepatitis C-related early-stage cirrhosis that predicts clinical deterioration. King LY, Canasto-Chibuque C, Johnson KB, Yip S, Chen X, Kojima K, Deshmukh M, Venkatesh A, Tan PS, Sun X, Villanueva A, Sangiovanni A, Nair V, Mahajan M, Kobayashi M, Kumada H, Iavarone M, Colombo M, Fiel MI, Friedman SL, Llovet JM, Chung RT, Hoshida Y. , PMID:25143343
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-54101.idf.txt
Sample and data relationshipE-GEOD-54101.sdrf.txt
Processed data (1)E-GEOD-54101.processed.1.zip
Additional data (1)E-GEOD-54101.additional.1.zip
Array designA-GEOD-14951.adf.txt
Links