Integrative biomarker analyses indicate etiological variations in hepatocellular carcinoma.

Zhu, Andrew X; Chen, David; He, Wei; Kanai, Masayuki; Voi, Maurizio; Chen, Li-Tzong; Daniele, Bruno; Furuse, Junji; Kang, Yoon-Koo; Poon, Ronnie T P; Vogel, Arndt; Chiang, Derek Y
Journal of hepatology
2016Apr ; 17 ( 5 ) :.
저자 상세정보
Zhu, Andrew X -
Chen, David -
He, Wei -
Kanai, Masayuki -
Voi, Maurizio -
Chen, Li-Tzong -
Daniele, Bruno -
Furuse, Junji -
Kang, Yoon-Koo -
Poon, Ronnie T P -
Vogel, Arndt -
Chiang, Derek Y -
BACKGROUND & AIMS: The purpose of this study was to determine whether biomarkers from baseline plasma and archival tissue specimens collected from patients enrolled in the EVOLVE-1 trial - a randomized phase 3 study of everolimus in hepatocellular carcinoma (HCC) - were associated with prognosis, etiology or ethnicity.

METHODS: Circulating plasma levels of bFGF, PLGF, VEGF, VEGF-D, c-Kit, collagen IV, sVEGFR1 and VEGFR2 were measured by ELISA (N=503). Protein levels of IGF-1R, c-Met, mTOR, Tsc2 were assayed by immunohistochemistry (N=125). Genomic DNA sequencing was conducted on a panel of 287 cancer-related genes (N=69).

RESULTS: Patients with baseline plasma concentrations of VEGF or sVEGFR1 above the cohort median had significantly shorter overall survival. These plasma biomarkers retained prognostic significance in a multivariate Cox regression model with geographic region, macroscopic vascular invasion and alpha fetoprotein AFP levels. Membranous c-Met protein levels were significantly lower for Asian patients, as well as for hepatitis B viral etiology. The prevalence of genetic changes were similar to previous reports, along with a trend towards higher PTEN and TSC2 mutations among Asians.

CONCLUSIONS: The angiogenesis biomarkers VEGF and sVEGFR1 were independent prognostic predictors of survival in patients with advanced HCC. Potential differences in c-Met and mTOR pathway activation between Asian and non-Asian patients should be considered in future clinical trials. LAY SUMMARY: Our study demonstrates that circulating angiogenesis biomarkers can predict the survival outcome in patients with advanced hepatocellular carcinoma independent of the clinical variables. There is etiology and ethnicity variation in molecular pathway activation in hepatocellular carcinoma, which should be considered for future clinical trial design of targeted therapy. CLINICAL TRIAL REGISTRATION NUMBER: NCT01035229. CI - Copyright ??2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Everolimus; Next-generation sequencing; PI-3 kinase pathway; Tsc2; c-Met; mTOR

주제명(Target field)
연구참여(Sample size)
질병특성(Condition Category)
연구설계(Study Design)
중재방법(Intervention Type)
중재명칭(Intervention Name)
Patients with baseline plasma concentrations of VEGF or sVEGFR1 above the cohort median had significantly shorter overall survival.
연구비지원(Fund Source)
근거수준평가(Evidence Hierarchy)
ICD 03