Yue Zhao1,2, Annelore Altendorf-Hofmann3, Ioannis Pozios4, Peter Camaj1,2, Therese Däberitz1, Xiaoyan Wang5, Hanno Niess5, Hendrik Seeliger4, Felix Popp1,2, Christopher Betzler1,2, Utz Settmacher3, Karl-Walter Jauch5, Christiane Bruns6,7, Thomas Knösel8. 1. Department of General, Visceral und Vascular Surgery, Otto-von-Guericke University, Leipziger Straße 44, Magdeburg, 39120, Germany. 2. General, Visceral and Cancer Surgery, University Hospital of Cologne, Cologne, Germany. 3. Department of General, Visceral und Vascular Surgery, Friedrich-Schiller University, Jena, Germany. 4. Department of General, Visceral und Vascular Surgery, Charite ́University Medical Center, Berlin, Germany. 5. Department of General, Visceral und Vascular Surgery, Ludwig-Maximilian-University (LMU), Munich, Germany. 6. Department of General, Visceral und Vascular Surgery, Otto-von-Guericke University, Leipziger Straße 44, Magdeburg, 39120, Germany. christiane.bruns@med.ovgu.de. 7. General, Visceral and Cancer Surgery, University Hospital of Cologne, Cologne, Germany. christiane.bruns@med.ovgu.de. 8. Institute of Pathology, Ludwig-Maximilian-University (LMU), Thalkirchnerstr. 36, Munich, 80337, Germany. Thomas.Knoesel@med.uni-muenchen.de.
Abstract
PURPOSE: Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) gene from IFITs family is one gene among hundreds of IFN-stimulated genes. The potential role of IFIT3 in cancer is scarcely understood. In addition, the clinical relevance of IFIT3 is not yet known in pancreatic ductal adenocarcinoma (PDAC). We evaluated the prognostic significance of this gene in PDAC patients. METHODS: The expression of IFIT3 was analyzed in pancreatic cancer cell lines with different metastatic potential (FG and L3.6pl) and one established gemcitabine resistant cell variant-L3.6plGres. Second, we analyzed the protein expression in tissue microarrays (TMA) from specimens of 254 radically resected patients with pancreatic adenocarcinoma. The prognostic relevance of IFIT3 was evaluated by the Kaplan-Meier and Cox regression analysis. RESULTS: L3.6pl cells with an aggressive capacity showed a significant higher expression of IFIT3 as compared to FG cells. IFIT3 was accumulated in gemcitabine resistant cells. Overexpression of IFIT3 increased the resistance of apoptosis against gemcitabine treatment. Patients who had high expression of IFIT3 (32%) and received chemotherapy had a statistically significant reduced survival in multivariate analysis. CONCLUSIONS: High expression of IFIT3 enhances anti-apoptotic activity and chemotherapy resistance of PDAC cells. High expression of IFIT3 was independently correlated to shorter patients' survival and may serve as a prognostic marker.
PURPOSE:Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) gene from IFITs family is one gene among hundreds of IFN-stimulated genes. The potential role of IFIT3 in cancer is scarcely understood. In addition, the clinical relevance of IFIT3 is not yet known in pancreatic ductal adenocarcinoma (PDAC). We evaluated the prognostic significance of this gene in PDAC patients. METHODS: The expression of IFIT3 was analyzed in pancreatic cancer cell lines with different metastatic potential (FG and L3.6pl) and one established gemcitabine resistant cell variant-L3.6plGres. Second, we analyzed the protein expression in tissue microarrays (TMA) from specimens of 254 radically resected patients with pancreatic adenocarcinoma. The prognostic relevance of IFIT3 was evaluated by the Kaplan-Meier and Cox regression analysis. RESULTS: L3.6pl cells with an aggressive capacity showed a significant higher expression of IFIT3 as compared to FG cells. IFIT3 was accumulated in gemcitabine resistant cells. Overexpression of IFIT3 increased the resistance of apoptosis against gemcitabine treatment. Patients who had high expression of IFIT3 (32%) and received chemotherapy had a statistically significant reduced survival in multivariate analysis. CONCLUSIONS: High expression of IFIT3 enhances anti-apoptotic activity and chemotherapy resistance of PDAC cells. High expression of IFIT3 was independently correlated to shorter patients' survival and may serve as a prognostic marker.
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