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RESEARCH PRODUCT
Neoangiogenesis-related genes are hallmarks of fast-growing hepatocellular carcinomas and worst survival. Results from a prospective study
Mariagrazia Del BuonoPaola LoriaTeresa PollicinoStefano ColopiElena BertoliniGuido MarzocchiStefano BallestriCristian CaporaliCalogero CammàBarbara LeiAimilia KarampatouGianluigi GiannelliFabiola MilosaErica VillaGiuseppe CabibboMarco EneaElena TurolaRosina Maria CritelliUmberto CilloGiorgio Enrico GerundaPatrizia PontissoNicola De MariaMaría L. Martínez-chantarPaola TodescaLuisa LosiLivia MaccioFilippo Schepissubject
AdultMale0301 basic medicinemedicine.medical_specialtyTime FactorsCarcinoma HepatocellularTime FactorMicroarrayHepatocellular carcinomamolecular carcinogenesisGastroenterologyliver imagingHEPATOCELLULAR CARCINOMA; LIVER IMAGING; MOLECULAR CARCINOGENESIS; MOLECULAR ONCOLOGY; Adult; Aged; Aged 80 and over; Carcinoma Hepatocellular; Disease Progression; Female; Humans; Liver Neoplasms; Male; Middle Aged; Neovascularization Pathologic; Prospective Studies; Survival Rate; Time Factors; Tumor Burden; Medicine (all); Gastroenterology03 medical and health sciencesmolecular oncology0302 clinical medicineHepatocellular carcinoma liver imaging molecular carcinogenesis molecular oncologyInternal medicinemedicineCarcinomaHumansDoubling timeProspective StudiesProspective cohort studySurvival rateAgedAged 80 and overNeovascularization Pathologicbusiness.industryProportional hazards modelLiver NeoplasmsGastroenterologyMiddle Agedmedicine.diseaseTumor BurdenSurvival RateProspective Studie030104 developmental biologyQuartileLiver Neoplasm030220 oncology & carcinogenesisHepatocellular carcinomaDisease ProgressionFemalebusinessHumandescription
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 6 weeks apart (no treatment in-between) to determine tumour volumes (V-0 and V-1) 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 621 days (mean, 107 +/- 91 days; median, 83 days) and were divided into quartiles: <= 53 days (n= 19), 54-82 days (n= 20), 83-110 days (n= 20) and >= 111 days (n= 19). Median survival according to doubling time was significantly lower for the first quartile versus the others (11 vs 41 months, 42, and 47 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2016-01-01 | Gut |