High expression of agrin is associated with tumor progression and poor prognosis in hepatocellular carcinoma

Abstract

The heparan sulfate proteoglycan agrin is known to accumulate in the context of hepatocellular carcinoma (HCC). Agrin is important for neoangiogenesis in HCC tissues, and is incorporated into newly formed vasculature, but exactly how agrin contributes to the pathology of HCC remains to be fully defined. We therefore examined the clinical relevance of agrin as it pertains to HCC progression and prognosis using tissue sections from a total of 313 HCC patients. We found that agrin expression was detectable in more HCC samples (25.4% vs. 77.1%; P < 0.05) compared to normal tissue controls. Agrin expression was notably linked to tumor size (P = 0.041) and metastasis (P = 0.034). The recurrence free survival rate of agrin-positive HCC patients was considerably lower than that of agrin-negative patients (P = 0.001). We further confirmed HCC survival to be independently correlated with tumor size, metastasis, microvascular invasion and edmondson Grade via a Cox regression analysis. Upregulation of Agrin may play a crucial role in HCC progression. Together our results suggest that Agrin has the potential to be used as a prognostic indicator in predicting HCC patient outcomes.