RNA-binding protein insulin-like growth factor II mRNA-binding protein 3 expression promotes tumor invasion and predicts early recurrence and poor prognosis in hepatocellular carcinoma
Open Access
- 9 June 2008
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hepatology
- Vol. 48 (4), 1118-1127
- https://doi.org/10.1002/hep.22459
Abstract
Insulin‐like growth factor II mRNA‐binding protein 3 (IMP3) is an RNA‐binding protein expressed in embryonic tissues and multiple cancers. To investigate the role of IMP3 in hepatocellular carcinoma (HCC), its protein expression in the surgically resected unifocal tumors of 377 HCC patients (296 men and 81 women) with ages ranging from 7 to 88 years (mean, 55.49 years) was analyzed by immunohistochemistry. IMP3 was expressed in 255 (67.6%) of 377 resected unifocal primary HCCs. IMP3 protein was predominantly expressed in tumor border and invasive front, and it was more abundant in the satellite nodules and tumor thrombi than in the main tumors. The expression correlated with high α‐fetoprotein (>200 ng/mL, P < 1 × 10−7), larger tumor size (>5 cm, P = 0.006), high tumor grade (P < 1 × 10−7), and high tumor stage with vascular invasion and various degrees of intrahepatic metastasis (P < 1 × 10−7). IMP3 expression predicted early tumor recurrence (P < 1 × 10−7) and was a strong indicator of poor prognosis (P < 0.0001). Depletion of IMP3 with RNA interference in HCC cell line HA22T caused a decrease in cell motility, invasion, and transendothelial migration. Microarray analysis revealed that IMP3 depletion was associated with downregulation of multiple genes involved in tumor invasion. Conclusion: Our results indicate that IMP3 plays an important role in tumor invasion and metastasis and is a strong prognostic factor for patients with HCC. (HEPATOLOGY 2008.)Keywords
This publication has 38 references indexed in Scilit:
- Clinical Significance of High Mobility Group A2 in Human Gastric Cancer and Its Relationship to let-7 MicroRNA FamilyClinical Cancer Research, 2008
- Overexpression of KIAA0101 Predicts High Stage, Early Tumor Recurrence, and Poor Prognosis of Hepatocellular CarcinomaClinical Cancer Research, 2007
- Hepatocellular Carcinoma: Epidemiology and Molecular CarcinogenesisGastroenterology, 2007
- The tumor suppressor microRNA let-7 represses the HMGA2 oncogeneGenes & Development, 2007
- Overexpression of tumour-associated trypsin inhibitor (TATI) enhances tumour growth and is associated with portal vein invasion, early recurrence and a stage-independent prognostic factor of hepatocellular carcinomaEuropean Journal Of Cancer, 2007
- Stathmin overexpression cooperates with p53 mutation and osteopontin overexpression, and is associated with tumour progression, early recurrence, and poor prognosis in hepatocellular carcinomaThe Journal of Pathology, 2006
- Down-regulation of CXCL5 Inhibits Squamous CarcinogenesisCancer Research, 2006
- Opposite Roles of Human Pancreatitis-Associated Protein and REG1A Expression in Hepatocellular Carcinoma: Association of Pancreatitis-Associated Protein Expression with Low-Stage Hepatocellular Carcinoma, β-Catenin Mutation, and Favorable PrognosisClinical Cancer Research, 2005
- Screening of DNA copy‐number aberrations in gastric cancer cell lines by array‐based comparative genomic hybridizationCancer Science, 2005
- Synthesis of Antihemophilic Factor Antigen by Cultured Human Endothelial CellsJCI Insight, 1973