Authors' Affiliations: Service d'Hépatologie, Service de Biochimie, Service de Radiologie, Hôpital Jean Verdier, AP-HP, Bondy; Université Paris 13-UFR SMBH/INSERM U698, Bobigny; Inserm, UMR-674, Génomique fonctionnelle des tumeurs solides, IUH; Labex Immuno-oncology, Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité; Département de Biostatistique, Hôpital Saint-Louis, AP-HP; Unité de Biostatistique et Epidémiologie clinique, Université Paris Diderot, INSERM, UMR-S717, Paris; Centre de Recherche Bichat Beaujon CRB3, Université Paris 7, INSERM, U773, Paris; and Lunginnov Campus de l'Institut Pasteur de Lille, France.
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.