PURPOSE: The aim of this study was to elucidate the role of HIF1A expression in hepatocellular carcinoma (HCC) and the corresponding non-malignant liver tissue and to correlate it with the clinical outcome of HCC patients after curative liver resection. METHODS: HIF1A expression was determined by quantitative RT-PCR in HCC and corresponding non-malignant liver tissue of 53 patients surgically treated for HCC. High-density gene expression analysis and pathway analysis was performed on a selected subset of patients with high and low HIF1A expression in the non-malignant liver tissue. RESULTS: HIF1A over-expression in the apparently non-malignant liver tissue was a predictor of tumor recurrence and survival. The estimated 1-year and 5-year disease-free survival was significantly better in patients with low HIF1A expression in the non-malignant liver tissue when compared to those patients with high HIF1 expression (88.9% vs. 67.9% and 61.0% vs. 22.6%, respectively, p = 0.008). Based on molecular pathway analysis utilizing high-density gene-expression profiling, HIF1A related molecular networks were identified that contained genes involved in cell migration, cell homing, and cell-cell interaction. CONCLUSION: Our study identified a potential novel mechanism contributing to prognosis of HCC. The deregulation of HIF1A and its related pathways in the apparently non-malignant liver tissue provides for a modulated environment that potentially enhances or allows for HCC recurrence after curative resection.
PURPOSE: The aim of this study was to elucidate the role of HIF1A expression in hepatocellular carcinoma (HCC) and the corresponding non-malignant liver tissue and to correlate it with the clinical outcome of HCCpatients after curative liver resection. METHODS:HIF1A expression was determined by quantitative RT-PCR in HCC and corresponding non-malignant liver tissue of 53 patients surgically treated for HCC. High-density gene expression analysis and pathway analysis was performed on a selected subset of patients with high and low HIF1A expression in the non-malignant liver tissue. RESULTS:HIF1A over-expression in the apparently non-malignant liver tissue was a predictor of tumor recurrence and survival. The estimated 1-year and 5-year disease-free survival was significantly better in patients with low HIF1A expression in the non-malignant liver tissue when compared to those patients with high HIF1 expression (88.9% vs. 67.9% and 61.0% vs. 22.6%, respectively, p = 0.008). Based on molecular pathway analysis utilizing high-density gene-expression profiling, HIF1A related molecular networks were identified that contained genes involved in cell migration, cell homing, and cell-cell interaction. CONCLUSION: Our study identified a potential novel mechanism contributing to prognosis of HCC. The deregulation of HIF1A and its related pathways in the apparently non-malignant liver tissue provides for a modulated environment that potentially enhances or allows for HCC recurrence after curative resection.
Authors: Yujin Hoshida; Augusto Villanueva; Masahiro Kobayashi; Judit Peix; Derek Y Chiang; Amy Camargo; Supriya Gupta; Jamie Moore; Matthew J Wrobel; Jim Lerner; Michael Reich; Jennifer A Chan; Jonathan N Glickman; Kenji Ikeda; Masaji Hashimoto; Goro Watanabe; Maria G Daidone; Sasan Roayaie; Myron Schwartz; Swan Thung; Helga B Salvesen; Stacey Gabriel; Vincenzo Mazzaferro; Jordi Bruix; Scott L Friedman; Hiromitsu Kumada; Josep M Llovet; Todd R Golub Journal: N Engl J Med Date: 2008-10-15 Impact factor: 91.245
Authors: S Rasheed; A L Harris; P P Tekkis; H Turley; A Silver; P J McDonald; I C Talbot; R Glynne-Jones; J M A Northover; T Guenther Journal: Br J Cancer Date: 2009-05-19 Impact factor: 7.640
Authors: Barbara Chiavarina; Ubaldo E Martinez-Outschoorn; Diana Whitaker-Menezes; Anthony Howell; Herbert B Tanowitz; Richard G Pestell; Federica Sotgia; Michael P Lisanti Journal: Cell Cycle Date: 2012-08-16 Impact factor: 4.534
Authors: Trina Das; Deborah L Diamond; Matthew Yeh; Sajida Hassan; Janine T Bryan; Jorge D Reyes; James D Perkins Journal: J Transplant Date: 2013-11-26