Osteopontin (OPN) plays an important role in the development, invasion, and metastasis of malignancies. Recently, several studies have reported that OPN enhances chemoresistance in small‐cell lung cancer and breast cancer by blocking caspase‐9 and caspase‐3‐dependent cell apoptosis. The aim of this study was to assess the value of OPN and caspase‐3 for predicting tumor recurrence after curative resection in hepatocellular carcinoma (HCC) patients. We found that OPN expression increased concordantly with increasing metastatic potential in human HCC cell lines, whereas caspase‐3 expression declined. In a tumor tissue microarray immunohistochemical analysis, we found that patients with higher levels of OPN and lower levels of caspase‐3 had a significantly poorer prognosis than patients with lower OPN and higher caspase‐3 levels. The combination of OPN and caspase‐3 expression thus served as an effective prognosticator. These findings suggest that OPN alone or in combination with caspase‐3 may act as an independent indicator for HCC patients after curative resection.

(Cancer Sci 2010; 101: 1314–1319)