Overexpression of osteopontin is associated with intrahepatic metastasis, early recurrence, and poorer prognosis of surgically resected hepatocellular cacinoma
Journal
Cancer
Journal Volume
98
Journal Issue
1
Pages
119-127
Date Issued
2003
Author(s)
Abstract
BACKGROUND. Intrahepatic 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. METHODS. OPN 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. RESULTS. Osteopontin 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). CONCLUSIONS. OPN 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. ? 2003 American Cancer Society.
SDGs
Other Subjects
alpha fetoprotein; messenger RNA; mutant protein; osteopontin; protein p53; article; cancer grading; cancer invasion; cancer recurrence; cancer surgery; cancer survival; correlation analysis; disease association; female; gene expression; human; human tissue; liver cell carcinoma; liver metastasis; liver resection; major clinical study; male; multivariate analysis; Northern blotting; portal vein; prediction; priority journal; prognosis; protein expression; reverse transcription polymerase chain reaction; tumor growth; Adolescent; Adult; Aged; Aged, 80 and over; Blotting, Northern; Carcinoma, Hepatocellular; Female; Gene Expression Regulation, Neoplastic; Humans; Liver Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Osteopontin; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm; Sialoglycoproteins; Survival Analysis
Type
journal article