Abstract
BackgroundHepatocellular carcinoma is an aggressive malignancy with poor prognosis and easy to recur even the tumor is totally removed by surgery. Portal vascular invasion is one of the major factors contributing to tumor recurrence and poor prognosis. However, why hepatocellular carcinoma is easy to grow into vessels is unclear.MethodsSurgical specimens from seven hepatocellular carcinoma patients with portal vein thrombosis and seven patients without vascular invasion were utilized to analyze protein expression by proteomic technique. The proteins in the tumors were separated by 2-dimensional electrophoresis. Protein patterns in the gels were recorded as digitalized images. The differences of expression in hepatocellular carcinoma with or without portal vein thrombosis were identified by mass spectrometry.ResultsClinically, the tumors with portal vein thrombosis were larger than those without portal vein thrombosis. The median survival time for the patients with portal vein thrombosis was much shorter [4 (ranged 2.5–47) vs. 53 (ranged 33–85) months, p = 0.002]. By analyzing the protein expression in cancer tissues with or without portal vein thrombosis, the differences of protein expression were mainly metabolic enzymes. Carbonic anhydrase I, betaine–homocysteine S-methyltransferase 1, fumarate hydratase, isovaleryl-CoA dehydrogenase, short-chain specific acyl-CoA dehydrogenase and arginase-1 were all down-regulated in the tumors with portal vein thrombosis.ConclusionMetabolic enzymes and cytosol carbonic anhydrases were downregulated in hepatocellular carcinoma with portal vein thrombus. The deficiency of metabolic enzymes and cytosol carbonic anhydrases may alter cellular metabolisms and acid–base balance in hepatocellular carcinoma, which may facilitate to invade portal vein.
Highlights
Hepatocellular carcinoma is an aggressive malignancy with poor prognosis and easy to recur even the tumor is totally removed by surgery
Characteristics of patients In this study, surgical specimens were taken from two groups of patients with different pathological presentation: Hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) and HCC without vascular invasion
The results showed that the patients with PVT were younger than the patients without vascular invasion
Summary
Hepatocellular carcinoma is an aggressive malignancy with poor prognosis and easy to recur even the tumor is totally removed by surgery. Portal vascular invasion is one of the major factors contributing to tumor recur‐ rence and poor prognosis. Hepatocellular carcinoma (HCC), the major primary liver cancer, is the sixth most common malignancy in the world [1]. This malignancy is aggressive and the prognosis is poor if the tumors are found at a late stage [2, 3]. Vascular invasion is always one of the most important risk factors of tumor recurrence either in liver resection or liver transplantation [4, 11, 12]. The Liver Cancer Study Group of Japan reported that the incidence of portal vein thrombosis (PVT) was 62% in autopsy [14]. It is essential to understand why HCC invades vessels
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