Upregulation of Spondin-2 protein expression correlates with poor prognosis in hepatocellular carcinoma

OBJECTIVE: The aim of this study was to measure the extracellular matrix protein Spondin-2 (SPON2) in hepatocellular carcinoma (HCC) tissues and to determine its potential value as a prognostic indicator by assessing its correlation with clinicopathological variables and survival. METHODS: SPON2 mRNA expression was assessed in 20 matched pairs of HCC and non-cancerous liver tissues by quantitative reverse transcription-polymerase chain reaction analysis. SPON2 protein expression was determined in 107 matched pairs of HCC and normal liver tissue by immunohistochemical staining of tissue microarrays. RESULTS: Analysis of patient tissues and Oncomine datasets showed that SPON2 mRNA and SPON2 protein expression were both significantly upregulated in HCC tissues, compared with non-cancerous liver tissue; moreover, both correlated significantly with tumor size. Kaplan-Meier analysis revealed that HCC patients who showed high levels of cytoplasmic SPON2 protein had poorer survival following curative resection, compared with HCC patients who exhibited low protein expression levels. Multivariate Cox regression analysis showed that tumor thrombus and SPON2 protein expression both independently correlated with reduced survival in HCC patients. CONCLUSION: Upregulated expression of SPON2 protein in tumor tissue could be an effective prognostic indicator for patients with HCC.