Clinical and Prognostic Implications of Plasma Insulin-Like Growth Factor-1 and Vascular Endothelial Growth Factor in Patients With Hepatocellular Carcinoma
Clinical and Prognostic Implications of Plasma Insulin-Like Growth Factor-1 and Vascular Endothelial Growth Factor in Patients With Hepatocellular Carcinoma
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DOI：
10.1200/jco.2011.36.0636
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发表时间：
2011-10-10
影响因子：
45.3
通讯作者：
Abbruzzese, James L.
中科院分区：
文献类型：
--
作者：
Kaseb, Ahmed O.;Morris, Jeffrey S.;Abbruzzese, James L.
目的肝硬化和肝细胞癌（HCC）共同形成了一种双疾病状态，影响HCC患者的生存率，并决定了临床试验中患者的治疗决策和预后分层。本研究的目的是改善HCC患者的预后分层。患者和方法我们前瞻性地收集了288例新发HCC患者的血浆样本和基线临床病理特征，并检测了血浆胰岛素样生长因子-1（IGF-1）和血管内皮生长因子（VEGF）水平。我们应用考克斯回归和对数秩检验评估IGF-1和VEGF与总生存期（OS）的相关性，Kaplan-Meier曲线估计OS，递归分割确定IGF-1和VEGF的最佳截止点。传统和分子巴塞罗那临床肝癌分类的预后能力进行了比较，使用c-index.Results较低的血浆IGF-1和较高的血浆VEGF水平显着相关的先进的临床病理参数和OS差，与最佳的切割点分别为26 ng/mL和450 pg/mL。低IGF-1和高VEGF的组合预测中位OS为2.7个月，而高IGF-1和低VEGF的患者为19个月（P <0.001），进一步改善了传统HCC分期的预后能力（P <0.001）。将IGF-1和VEGF整合到HCC分期中显着增强了患者的预后分层。如果得到验证，这些结果可能被证明是有用的，在这些患者中设计个性化的管理方法的策略。
Purpose Cirrhosis and hepatocellular carcinoma (HCC) together form a two-disease state that affects survival of patients with HCC and dictates treatment decisions and prognostic stratification of patients in clinical trials. The study objective was to improve prognostic stratification of patients with HCC.Patients and Methods We prospectively collected plasma samples and baseline clinicopathologic features from 288 new patients with HCC, and plasma insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) levels were tested. We applied Cox regression and log-rank tests to assess association of IGF-1 and VEGF with overall survival (OS), Kaplan-Meier curves to estimate OS, and recursive partitioning to determine optimal cutoff points for IGF-1 and VEGF. Prognostic ability of conventional and molecular Barcelona Clinic Liver Cancer classifications was compared using the c-index.Results Lower plasma IGF-1 and higher plasma VEGF levels significantly correlated with advanced clinicopathologic parameters and poor OS, with optimal cut points of 26 ng/mL and 450 pg/mL, respectively. The combination of low IGF-1 and high VEGF predicted median OS of 2.7 months compared with 19 months for patients with high IGF-1 and low VEGF (P < .001), further refining the prognostic ability of conventional HCC staging (P < .001).Conclusion Baseline levels of plasma IGF-1 and VEGF correlated significantly with survival in patients with HCC. Integrating IGF-1 and VEGF into HCC staging significantly enhanced prognostic stratification of patients. If validated, these results may prove to be useful in designing strategies to personalize management approaches among these patients.