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.
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Acknowledgements
The authors appreciated Mrs. Andrea Sendelhofert for her expertise and technical assistance in tissue microarray immunohistochemistry staining, Dr Gerald Assmann for his support on paraffin samples collection and Dr. Gabriele Schubert-Fritschle from the Munich tumor registry for assistance in completing the follow-up information.
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Zhao, Y., Altendorf-Hofmann, A., Pozios, I. et al. Elevated interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) is a poor prognostic marker in pancreatic ductal adenocarcinoma. J Cancer Res Clin Oncol 143, 1061–1068 (2017). https://doi.org/10.1007/s00432-017-2351-4
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DOI: https://doi.org/10.1007/s00432-017-2351-4