[43] OSTEOPONTIN PROTEIN WAS immunohistochemically labeled in 40–

[43] OSTEOPONTIN PROTEIN WAS immunohistochemically labeled in 40–55% of HCC,[11, 44-46] and OPN mRNA was overexpressed in 55% of HCC.[12] The immunohistochemical staining

and RNA in situ analysis were observed in the cytoplasm of HCC cells, but not in nuclei.[11, 12, 44] OPN positive HCC cells were selleck compound scattered in the periphery of cancer nodules adjacent to stromal cells, or dispersed in the cancer nodules.[11, 46, 47] OPN protein and/or mRNA overexpression was significantly associated with large size,[12, 45] late tumor stage,[12, 48] poor differentiation,[12, 45, 46, 48] capsular infiltration,[11, 44, 45] vascular invasion,[44, 46] lymph node invasion[44] and intrahepatic metastasis[12, 13, 46] of HCC. Plasma OPN levels were significantly higher in patients with HCC than in patients with chronic liver diseases without HCC, and healthy controls.[47, 49] In patients after curative resection of hepatitis B virus (HBV)-related HCC, plasma OPN levels significantly

decreased after a transient fluctuation, and increased again at the time of tumor recurrence.[50] As a marker for the diagnosis of HCC in patients with cirrhosis, plasma OPN level had a greater area under curve (AUC) value than α-fetoprotein (AFP)[47, 49, 51] and protein induced by vitamin K absence/antagonist-II[47] by receiver–operator curve (ROC) analysis. Furthermore, the combination of OPN and AFP levels enhanced sensitivity and specificity in detecting HCC.[51] Moreover, plasma OPN levels were reported to be useful as a prognostic http://www.selleckchem.com/products/Roscovitine.html factor after liver resection

or transplantation in patients with HCC of tumor–node–metastasis (TNM) find more stage I, II or III.[48, 52] In a prospective study, TNM stage and plasma OPN level measured prior to tumor resection were highly significant predictors of overall survival (OS) and disease-free survival (DFS) in patients with HCC in China.[48] Preoperative plasma OPN level and Edmondson’s grade were also identified as independent predictors for prognostic factor for OS and DFS in patients with TNM stage I of HBV-related HCC.[52] Increased expression of OPN protein in HCC was also shown to be an independent predictor of poor OS and/or poor DFS in patients undergoing liver transplantation[53] and resection of HCC.[44, 54, 55] Finally, a meta-analysis revealed high OPN expression in HCC predicted poor OS (hazard ratio, 1.37; 95% CI, 1.21–1.55) and DFS (hazard ratio, 1.62; 95% CI, 1.24–2.11) of HCC after liver resection, liver transplantation or transarterial chemoembolization.[56] It has been reported that OPN plays significant roles in the metastasis of HCC in vivo and in vitro. However, the effects of OPN on the growth of HCC cells were controversial. In nude mice, s.c.

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