Decreased expression of osteopontin is related to tumor aggressiveness and clinical outcome of intrahepatic cholangiocarcinoma

Abstract

Background: Osteopontin (OPN) is known to be a secreted adhesive glycoprotein. Recent studies have reported that the overexpression of OPN is correlated with tumorigenesis, tumor aggressiveness, and poor prognosis in several types of human cancer. The aim of this study was to determine whether the expression of OPN in cases of intrahepatic cholangiocarcinoma (ICC) indicates the clinical outcome.

Methods: The expression of OPN protein was investigated immunohistochemically in surgically resected specimens from 73 patients, and the level of OPN mRNA was also examined by quantitative real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) in nine samples of ICC. We examined the correlation between the expression of OPN and the clinicopathological factors, including overall survival, in patients with ICC.

Results: We detected the positive expression of OPN protein in 31 of 73 (42.5%) of the primary ICCs. Negative expression of OPN protein was significantly related to lymphatic permeation, perineural invasion, intrahepatic metastasis, and lymph node metastasis (P=0.0029, 0.0072, 0.0134, and 0.0101, respectively). Overall survival was significantly lower among the patients with a negative expression of OPN than it was among those with a positive expression of OPN. The negative expression of OPN protein and the lower levels of OPN mRNA were statistically significant (P=0.0139).

Conclusions: Decreased expression of OPN is considered to be a reliable indicator of tumor aggressiveness and clinical outcome in patients with ICC.