Service d'Hépatologie, Hôpital Jean Verdier, AP-HP, Bondy, France.
Cancer Epidemiol Biomarkers Prev. 2013 Aug;22(8):1343-52. doi: 10.1158/1055-9965.EPI-13-0179. Epub 2013 Jun 18.
Proteoglycans are involved in neoangiogenesis and transduction of oncogenic signals, two hallmarks of carcinogenesis.
This study sought to assess the prognostic value of serum levels of three proteoglycans (endocan, syndecan-1, and glypican-3) and VEGF in 295 patients with alcoholic cirrhosis: 170 without hepatocellular carcinoma, 58 with early hepatocellular carcinoma, and 67 with advanced hepatocellular carcinoma at inclusion. We analyzed the association between proteoglycan levels and prognosis using Kaplan-Meier and Cox methods.
Serum levels of the three proteoglycans and VEGF were increased in patients with advanced hepatocellular carcinoma compared with those without hepatocellular carcinoma or with early hepatocellular carcinoma. In multivariate analysis, high levels of serum endocan (>5 ng/mL) were independently associated with death [HR, 2.84; 95% confidence interval (CI,) 1.18-6.84; P = 0.02], but not with hepatocellular carcinoma occurrence, in patients without hepatocellular carcinoma at baseline. High serum endocan (>5 ng/mL) and syndecan-1 (>50 ng/mL) levels were significantly associated with greater risk of tumor recurrence (P = 0.025) in patients with early hepatocellular carcinoma treated by radiofrequency ablation. In patients with advanced hepatocellular carcinoma, high serum levels of endocan (P = 0.004) and syndecan-1 (P = 0.006) were significantly associated with less favorable overall survival. However, only a high level of serum syndecan-1 (>50 ng/mL) was independently associated with greater risk of death (HR, 6.21 95% CI, 1.90-20.30; P = 0.0025).
Serum endocan and syndecan-1 are easily assessable prognostic serum biomarkers of overall survival in alcoholic cirrhosis with and without hepatocellular carcinoma.
These new biomarkers will be useful to manage patients with hepatocellular carcinoma developed on alcoholic cirrhosis.
蛋白聚糖参与新生血管形成和致癌信号转导，这是癌变的两个标志。
本研究旨在评估 295 例酒精性肝硬化患者血清中三种蛋白聚糖（内皮下蛋白、连接蛋白-1 和糖蛋白-3）和 VEGF 的水平对预后的影响：170 例无肝细胞癌，58 例早期肝细胞癌，67 例晚期肝细胞癌。我们使用 Kaplan-Meier 和 Cox 方法分析了蛋白聚糖水平与预后之间的关系。
与无肝细胞癌或早期肝细胞癌患者相比，晚期肝细胞癌患者的三种蛋白聚糖和 VEGF 血清水平升高。多变量分析显示，血清内皮下蛋白水平升高（>5ng/ml）与死亡独立相关[风险比，2.84；95%置信区间（CI），1.18-6.84；P=0.02]，但与基线时无肝细胞癌患者的肝细胞癌发生无关。血清内皮下蛋白（>5ng/ml）和连接蛋白-1（>50ng/ml）水平升高与接受射频消融治疗的早期肝细胞癌患者肿瘤复发风险显著增加相关（P=0.025）。在晚期肝细胞癌患者中，血清内皮下蛋白（P=0.004）和连接蛋白-1（P=0.006）水平升高与总生存时间较差显著相关。然而，只有血清连接蛋白-1（>50ng/ml）水平升高与死亡风险增加独立相关（风险比，6.21；95%CI，1.90-20.30；P=0.0025）。
血清内皮下蛋白和连接蛋白-1是酒精性肝硬化合并和不合并肝细胞癌患者总生存的易于评估的预后血清标志物。
这些新的生物标志物将有助于管理酒精性肝硬化发展为肝细胞癌的患者。
