Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), Faculty of Medicine, Toho University School of Medicine, 6-11-1, Omorinishi, Ota-ku, Tokyo, 143-8541, Japan.
Anticancer Res. 2013 Mar;33(3):1013-21.
Vascular endothelial growth factor (VEGF) is a primary driving force for both physiological and pathological angiogenesis, and its overexpression has been found in hepatocellular carcinoma (HCC). The aim of this study was to retrospectively clarify the usefulness of serum VEGF levels as a tumor marker in patients with hepatitis C virus (HCV)-related liver cirrhosis (CLC) and HCC.
The patients with CLC were divided into three groups: 28 patients without HCC (CLC group), 11 patients with HCC (HCC group), and 48 patients with advanced HCC (aHCC group). The control group consisted of 37 patients with chronic HCV.
When the relation of serum VEGF to liver function was assessed, there was no significant difference of VEGF levels between the control group and the CLC group. When serum VEGF levels were assessed in relation to the presence of HCC, the VEGF levels of the HCC group and aHCC group were found to be significantly higher than that of the control group, while there was no significant difference between the control group and the CLC group. For the detection of cancer, serum VEGF had the largest area under the curve (AUC) and the highest accuracy when we employed the cut-off value obtained by receiver operating characteristic (ROC) analysis using the Youden index. Evaluation of various tumor markers in the aHCC group showed that the serum levels of α-fetoprotein (AFP) were higher in patients with infiltrating tumors than in patients with multiple discrete nodules or confluent multinodular tumors, while there were no significant differences in the serum levels of VEGF, Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and des-γ-carboxy prothrombin. There were no significant differences on the serum levels of all four markers between tumor stages, but serum VEGF was higher in patients with vascular invasion than in those without vascular invasion.
The present findings suggest that the serum levels of VEGF might be a useful predictor of the presence of HCC in patients with CLC, while serum levels of AFP and VEGF can predict the tumor type and vascular invasion, respectively.
血管内皮生长因子（VEGF）是生理和病理血管生成的主要驱动力，其在肝细胞癌（HCC）中过度表达。本研究旨在回顾性阐明血清 VEGF 水平作为丙型肝炎病毒（HCV）相关肝硬化（CLC）和 HCC 患者肿瘤标志物的有用性。
将 CLC 患者分为三组：28 例无 HCC（CLC 组）、11 例 HCC（HCC 组）和 48 例晚期 HCC（aHCC 组）。对照组由 37 例慢性 HCV 患者组成。
当评估血清 VEGF 与肝功能的关系时，对照组和 CLC 组之间 VEGF 水平无显著差异。当评估血清 VEGF 与 HCC 存在的关系时，HCC 组和 aHCC 组的 VEGF 水平明显高于对照组，而对照组和 CLC 组之间无显著差异。对于癌症的检测，当使用 ROC 分析获得的最佳截断值（Youden 指数）时，血清 VEGF 的曲线下面积（AUC）最大，准确率最高。在 aHCC 组中评估各种肿瘤标志物，发现浸润性肿瘤患者的血清 AFP 水平高于多发性离散结节或融合多结节肿瘤患者，但 VEGF、 Lens culinaris agglutinin-reactive fraction of AFP（AFP-L3）和 des-γ-carboxy prothrombin 的血清水平无显著差异。在肿瘤分期方面，四种标志物的血清水平均无显著差异，但血管侵犯患者的血清 VEGF 水平高于无血管侵犯患者。
本研究结果表明，血清 VEGF 水平可能是 CLC 患者 HCC 存在的有用预测指标，而 AFP 和 VEGF 血清水平可分别预测肿瘤类型和血管侵犯。
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