Elevated interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) is a poor prognostic marker in pancreatic ductal adenocarcinoma
Elevated interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) is a poor prognostic marker in pancreatic ductal adenocarcinoma
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干扰素诱导蛋白四三肽重复序列 3 (IFIT3) 升高是胰腺导管腺癌的不良预后标志物
DOI：
10.1007/s00432-017-2351-4
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发表时间：
2017
影响因子：
3.6
通讯作者：
Thomas Knösel
中科院分区：
文献类型：
--
作者：
Yue Zhao;Annelore Altendorf-Hofmann;Ioannis Pozios;Peter Camaj;Therese Däberitz;Xiaoyan Wang;Hanno Niess;Hendrik Seeliger;Felix Popp;Christopher Betzler;Utz Settmacher;Karl-Walter Jauch;Christiane Bruns;Thomas Knösel
IFIT3 （tetratricopeptide repeats 3）基因是IFITs家族的干扰素诱导蛋白，是数百个干扰素刺激基因之一。IFIT3在癌症中的潜在作用几乎不为人所知。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。方法分析IFIT3在不同转移潜能的胰腺癌细胞系（FG和L3.6pl）和一种已建立的吉西他滨耐药细胞变体l3.6 plgres中的表达。其次，我们分析了254例胰腺腺癌根治患者标本的组织微阵列（TMA）蛋白表达。结果具有侵袭能力的sl3.6 pl细胞中IFIT3的表达明显高于FG细胞。IFIT3在吉西他滨耐药细胞中积累。IFIT3的过表达增加了细胞凋亡对吉西他滨治疗的耐药性。多因素分析显示，IFIT3高表达（32%）并接受化疗的患者生存率有统计学意义的降低。结论IFIT3的高表达增强了PDAC细胞的抗凋亡活性和化疗耐药性。IFIT3的高表达与较短的患者生存期独立相关，可作为预后指标。
PurposeInterferon-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.MethodsThe 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.ResultsL3.6pl 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.ConclusionsHigh 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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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
5.4
作者：
Niess, Hanno;Camaj, Peter;Bruns, Christiane J.
通讯作者：
Bruns, Christiane J.
影响因子：
4.3
作者：
Polistina, Francesco;Di Natale, Giuseppe;Frego, Mauro
通讯作者：
Frego, Mauro
影响因子：
3.8
作者：
Ferrone, Cristina R.;Pieretti-Vanmarcke, Rafael;Bloom, Jordan P.;Zheng, Hui;Szymonifka, Jackye;Wargo, Jennifer A.;Thayer, Sarah P.;Lauwers, Gregory Y.;Deshpande, Vikram;Mino-Kenudson, Mari;Fernandez-del Castillo, Carlos;Lillemoe, Keith D.;Warshaw, Andrew L.
通讯作者：
Warshaw, Andrew L.