Prognostic significance of osteopontin in hepatitis B virus-related hepatocellular carcinoma

Osteopontin (OPN) is known to be associated with metastasis in many types of cancers. Since OPN is a highly phosphorylated and glycosylated protein, the modification after transcription is very important to its function. In hepatocellular carcinoma (HCC), the elevated expression of OPN at mRNA levels and its relationship with metastasis and poorer prognosis of the patients have been reported. However, the prognostic impact of OPN at protein levels on the patients with hepatitis B virus (HBV)-related HCC after hepatectomy is still limited.

The expression of OPN was examined at protein level by using immunohistochemistry in 72 patients who underwent hepatectomy for HBV-related HCC, and its prognostic significance in disease-free and overall survival of the patients was also analyzed by log-rank test and multivariate Cox regression analyses.

Thirty-nine of 72 (54.17%) HBV-related HCC specimens were positive for OPN with cytoplasmic staining. OPN was highly expressed in the specimens with capsular infiltration compared to those without (P<0.05), and also was significantly related with portal vein invasion (P<0.01) and lymph node invasion (P<0.01). The mean disease-free survival (DFS) was only 13.55+/-14.77 months when the HBV-related HCC specimens highly expressed OPN compared to 36.00+/-18.68 months for those with low expression (P<0.001). The overall survival (OS) of the patients was 18.63+/-17.28 months when the HCC over-expressed OPN compared to 42.59+/-16.85 months for HCC with the low expressed OPN (P<0.001). Multivariate analysis showed that OPN over-expression was the strongest independent adverse prognostic factor for both DFS (P=0.01) and OS (P=0.014).

OPN over-expression was closely related to capsular infiltration, venous invasion, lymph node metastasis, and also with worse prognosis, suggesting that OPN might be deemed as a useful molecular marker for predicting the prognosis of HCC.