HIWI is associated with prognosis in patients with hepatocellular carcinoma after curative resection
Open Access
- 11 October 2011
- Vol. 118 (10), 2708-2717
- https://doi.org/10.1002/cncr.26524
Abstract
BACKGROUND: PIWI protein family was found to play an important role in stem cell self‐renewal. Overexpression of HIWI, the human homolog of PIWI family proteins, was found in several solid tumors, although the role of HIWI in hepatocellular carcinoma (HCC) and its prognostic value remain unclear. METHODS: HIWI expression was measured in stepwise metastatic HCC cell lines (HCCLM3, MHCC97H, MHCC97L, SMMC7721, and HepG2), the normal liver cell line (L02), and HCC tissue samples (n = 20). Proliferation and invasion were investigated in HCC cell lines undergoing HIWI target small interfering RNA transfection. Also explored was HIWI expression in HCC tissue microarrays (n = 168) for survival analysis. RESULTS: Levels of HIWI protein and mRNA were up‐regulated in highly metastatic HCC cell lines (HCCLM3, MHCC97H, and MHCC97L), whereas their proliferation and invasion significantly decreased after depletion of HIWI. Intratumoral HIWI expression was higher than that of peritumoral tissue (P < .001) and positively associated with proliferating cell nuclear antigen expression (P < .001). Positive expression of intratumoral HIWI was associated with larger tumor size (P = .047) and intrahepatic metastasis (P = .027) and was an independent risk factor for overall survival (P = .007) and recurrence‐free survival (P = .036), particularly in patients with low serum α‐fetoprotein and low Edmondson‐Steiner grade. CONCLUSIONS: HIWI may play a key role in HCC proliferation and metastasis and can be a potential prognostic factor for HCC after curative resection, particularly with well‐differentiated HCC. Cancer 2011. © 2011 American Cancer Society.Keywords
This publication has 30 references indexed in Scilit:
- Role of cancer stem cells in hepatocarcinogenesisGenome Medicine, 2011
- Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008International Journal of Cancer, 2010
- Expression of HIWI in human esophageal squamous cell carcinoma is significantly associated with poorer prognosisBMC Cancer, 2009
- A System of Classifying Microvascular Invasion to Predict Outcome After Resection in Patients With Hepatocellular CarcinomaGastroenterology, 2009
- The stem cell-associated Hiwi gene in human adenocarcinoma of the pancreas: expression and risk of tumour-related deathBritish Journal of Cancer, 2008
- Argonautes confront new small RNAsCurrent Opinion in Chemical Biology, 2007
- Proline-Directed Protein Kinase FA Is a Powerful and Independent Prognostic Predictor for Progression and Patient Survival of Hepatocellular CarcinomaJournal of Clinical Oncology, 2006
- Recent progress in predictive biomarkers for metastatic recurrence of human hepatocellular carcinoma: a review of the literatureZeitschrift für Krebsforschung und Klinische Onkologie, 2004
- pRb2/p130, Vascular Endothelial Growth Factor, p27(KIP1), and Proliferating Cell Nuclear Antigen Expression in Hepatocellular CarcinomaClinical Cancer Research, 2004
- Identification of eight members of the Argonaute family in the human genome☆Genomics, 2003