Zhao Yue, Altendorf-Hofmann Annelore, Pozios Ioannis, Camaj Peter, Däberitz Therese, Wang Xiaoyan, Niess Hanno, Seeliger Hendrik, Popp Felix, Betzler Christopher, Settmacher Utz, Jauch Karl-Walter, Bruns Christiane, Knösel Thomas
Department of General, Visceral und Vascular Surgery, Otto-von-Guericke University, Leipziger Straße 44, Magdeburg, 39120, Germany.
General, Visceral and Cancer Surgery, University Hospital of Cologne, Cologne, Germany.
J Cancer Res Clin Oncol. 2017 Jun;143(6):1061-1068. doi: 10.1007/s00432-017-2351-4. Epub 2017 Feb 17.
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.
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.
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.
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.
干扰素诱导的四肽重复序列蛋白3（IFIT3）基因是干扰素刺激基因家族数百个基因中的一个。IFIT3在癌症中的潜在作用鲜为人知。此外，IFIT3在胰腺导管腺癌（PDAC）中的临床相关性尚不清楚。我们评估了该基因在PDAC患者中的预后意义。
分析了具有不同转移潜能的胰腺癌细胞系（FG和L3.6pl）以及一种已建立的吉西他滨耐药细胞变体-L3.6plGres中IFIT3的表达。其次，我们分析了254例接受根治性切除的胰腺腺癌患者标本的组织微阵列（TMA）中的蛋白表达。通过Kaplan-Meier和Cox回归分析评估IFIT3的预后相关性。
与FG细胞相比，具有侵袭能力的L3.6pl细胞中IFIT3的表达显著更高。IFIT3在吉西他滨耐药细胞中积累。IFIT3的过表达增加了对吉西他滨治疗的凋亡抗性。在多变量分析中，IFIT3高表达（32%）且接受化疗的患者生存率有统计学意义的降低。
IFIT3的高表达增强了PDAC细胞的抗凋亡活性和化疗抗性。IFIT3的高表达与患者较短的生存期独立相关，可作为一种预后标志物。
