Overexpression of osteopontin is associated with intrahepatic metastasis, early recurrence, and poorer prognosis of surgically resected hepatocellular carcinoma

Abstract

BACKGROUNDIntrahepatic metastasis via portal vein spread is an important feature and a crucial unfavorable prognostic factor of hepatocellular carcinoma (HCC). To identify the molecular factors for tumor progression, the authors used differential display (DD) to analyze aberrant gene expression in HCC. The goal of the current study was to elucidate the clinicopathologic and prognostic significance of osteopontin (OPN) in HCC progression.METHODSOPN mRNA levels, which were increased preferentially in HCC in a DD assay and verified with Northern blotting, were measured in 240 surgically removed, unifocal, primary HCCs using the reverse transcription–polymerase chain reaction at the exponential phase. OPN mRNA expression was correlated with clinicopathologic features, particularly portal vein invasion, early tumor recurrence, and prognosis.RESULTSOsteopontin mRNA was overexpressed in 133 tumors (55%). The OPN overexpression was associated closely with α‐fetoprotein elevation (P = 0.001), p53 mutation (P = 0.021), larger tumors (P = 0.002), high‐grade HCC (P < 0.001), late‐stage HCC (P < 0.001), early tumor recurrence and/or metastasis (P = 0.003), and a lower 10‐year survival rate (P = 0.00013). Multivariate analysis revealed that tumor stage and early tumor recurrence were crucial prognostic factors. In early‐stage HCC, which has no vascular invasion and a lower early tumor recurrence than late‐stage HCC, OPN mRNA overexpression predicted a higher early recurrence rate (P = 0.003).CONCLUSIONSOPN mRNA overexpression was correlated closely with high‐grade, late‐stage, and early tumor recurrence, which lead to poorer prognosis. Osteopontin overexpression might serve as an unfavorable prognostic factor and a useful marker for predicting early recurrence in early‐stage HCC. Cancer 2003;98:119–27. © 2003 American Cancer Society.DOI 10.1002/cncr.11487

High α‐fetoprotein level correlates with high stage, early recurrence and poor prognosis of hepatocellular carcinoma: Significance of hepatitis virus infection, age, p53 and β‐catenin mutations

“…39 Here we showed that tumor stage closely correlated with patient's survival (p Ͻ 0.0001), and minute HCC (Յ 2 cm) with encapsulation and no vascular invasion was a unique group of HCC with an excellent prognosis (Fig. 2).…”

Performance of diagnostic biomarkers in predicting liver fibrosis among hepatitis C virus-infected Egyptian children

“…OPN is an ECM protein that is considered as the third marker for matrix deposition (Pan et al 2003). Abu El Makarem et al (2011) found a significant elevation in OPN levels in patients with HCV-related HCC.…”

“…OPN is an integrin-binding glycophosphoprotein that is expressed by several cell types and especially by transformed malignant epithelial cells. Additionally, OPN is believed to be involved in many physiological cellular functionsespecially in the regulation of migration, invasion and thus metastasis as well as in the survival of tumour cells (Pan et al 2003). doi: 10.1590/0074-0276130139These biomarkers have been analysed individually and in combination to assess the severity and progression of hepatic fibrosis and to follow-up changes related to viral treatment (Saitou et al 2005, Sanvisens et al 2009, Parkes et al 2011).…”

Role of osteopontin in tumour progression

“…In contrast, in a study of a series of 240 hepatocellular carcinomas, elevated OPN RNA levels were associated with high grade, late stage and early recurrence, which are all associated with poor patient prognosis (Pan et al, 2003). In an expression array study of 60 colorectal tumours, representing a range of stages from adenomas, Astler Collier stages B, C and D, and liver metastases, OPN was identified as the lead marker that was most consistently upregulated with tumour progression (Agrawal et al, 2002).…”