Neoangiogenesis-related genes are hallmarks of fast-growing hepatocellular carcinomas and worst survival. Results from a prospective study.
Gut
; 65(5): 861-9, 2016 May.
Article
em En
| MEDLINE
| ID: mdl-25666192
ABSTRACT
OBJECTIVE:
The biological heterogeneity of hepatocellular carcinoma (HCC) makes prognosis difficult. We translate the results of a genome-wide high-throughput analysis into a tool that accurately predicts at presentation tumour growth and survival of patients with HCC.DESIGN:
Ultrasound surveillance identified HCC in 78 (training set) and 54 (validation set) consecutive patients with cirrhosis. Patients underwent two CT scans 6â weeks apart (no treatment in-between) to determine tumour volumes (V0 and V1) and calculate HCC doubling time. Baseline-paired HCC and surrounding tissue biopsies for microarray study (Agilent Whole Human Genome Oligo Microarrays) were also obtained. Predictors of survival were assessed by multivariate Cox model.RESULTS:
Calculated tumour doubling times ranged from 30 to 621â days (mean, 107±91â days; median, 83â days) and were divided into quartiles ≤53â days (n=19), 54-82â days (n=20), 83-110â days (n=20) and ≥111â days (n=19). Median survival according to doubling time was significantly lower for the first quartile versus the others (11 vs 41â months, 42, and 47â months, respectively) (p<0.0001). A five-gene transcriptomic hepatic signature including angiopoietin-2 (ANGPT2), delta-like ligand 4 (DLL4), neuropilin (NRP)/tolloid (TLL)-like 2 (NETO2), endothelial cell-specific molecule-1 (ESM1), and nuclear receptor subfamily 4, group A, member 1 (NR4A1) was found to accurately identify rapidly growing HCCs of the first quartile (ROC AUC 0.961; 95% CI 0.919 to 1.000; p<0.0001) and to be an independent factor for mortality (HR 3.987; 95% CI 1.941 to 8.193, p<0.0001).CONCLUSIONS:
The hepatic five-gene signature was able to predict HCC growth in individual patient and the consequent risk of death. This implies a role of this molecular tool in the future therapeutic management of patients with HCC. TRIAL REGISTRATION NUMBER ClinicalTrials.gov Identifier NCT01657695.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Hepatocelular
/
Neoplasias Hepáticas
Tipo de estudo:
Observational_studies
/
Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
/
Aged80
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Gut
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Itália