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
Journal
Hepatology
Journal Volume
48
Journal Issue
4
Pages
1118-1127
Date Issued
2008
Author(s)
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. Copyright ? 2008 by the American Association for the Study of Liver Diseases.
SDGs
Other Subjects
alpha fetoprotein; beta catenin; insulin like growth factor 2 messenger RNA binding protein 3; protein p53; RNA; RNA binding protein; unclassified drug; high mobility group A2 protein; IMP 3 protein, human; IMP-3 protein, human; RNA binding protein; tumor protein; adolescent; adult; aged; animal tissue; article; cancer cell culture; cancer grading; cancer invasion; cancer recurrence; cancer staging; cell migration; cell motility; cell proliferation; down regulation; endothelium; female; gene mutation; genetic transfection; histopathology; human; human cell; immunohistochemistry; liver cell carcinoma; liver resection; major clinical study; male; metastasis; microarray analysis; nonhuman; nucleotide sequence; plasmid; prediction; priority journal; prognosis; protein depletion; protein expression; protein localization; real time polymerase chain reaction; RNA interference; RNA isolation; school child; tissue distribution; tumor thrombus; tumor volume; Western blotting; cell motion; child; Kaplan Meier method; liver cell carcinoma; liver tumor; metabolism; middle aged; multivariate analysis; pathology; prediction and forecasting; retrospective study; tumor cell line; tumor recurrence; Adolescent; Adult; Aged; Aged, 80 and over; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Movement; Child; Female; HMGA2 Protein; Humans; Kaplan-Meiers Estimate; Liver Neoplasms; Male; Middle Aged; Multivariate Analysis; Neoplasm Invasiveness; Neoplasm Proteins; Neoplasm Recurrence, Local; Neoplasm Staging; Predictive Value of Tests; Prognosis; Retrospective Studies; RNA-Binding Proteins
Type
journal article