Expression and Clinical Significance of Protein Kinase RNA-Like Endoplasmic Reticulum Kinase and Phosphorylated Eukaryotic Initiation Factor 2α in Pancreatic Ductal Adenocarcinoma.
Expression and Clinical Significance of Protein Kinase RNA-Like Endoplasmic Reticulum Kinase and Phosphorylated Eukaryotic Initiation Factor 2α in Pancreatic Ductal Adenocarcinoma.
复制标题
蛋白激酶RNA样内质网激酶和磷酸化真核起始因子2α在胰管腺癌中的表达和临床意义。
DOI：
10.1097/mpa.0000000000001248
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发表时间：
2019
期刊：
影响因子：
2.9
通讯作者：
Katz,MatthewHG
中科院分区：
文献类型：
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作者：
Wang,EricM;Akasaka,Hironari;Zhao,Jun;Varadhachary,GauriR;Lee,JeffreyE;Maitra,Anirban;Fleming,JasonB;Hung,Mien-Chie;Wang,Huamin;Katz,MatthewHG
目的内质网应激和随后的蛋白激酶 R 样内质网激酶 (PERK) 对真核起始因子 2α (eIF2α) 的磷酸化在胰腺导管腺癌 (PDAC) 的发生和化疗耐药中发挥重要作用。然而，磷酸化 eIF2α (p-eIF2α) 和 PERK 在 PDAC 中的表达和意义尚未得到检验。方法我们检测了 84 例 PDAC 中的 p-eIF2α 和 PERK 表达，并通过免疫组织化学和蛋白质印迹配对正常胰腺样本，并将结果与临床病理参数和生存率相关联。结果 PDAC 中的平均 PERK H 评分为 140.8，而正常胰腺样本为 82.1。胰腺（P<0.001）。 p-eIF2α 在 56% 的 PDAC 中高表达，而在正常胰腺中这一比例为 7.6%（P<0.001）。高 PERK 和 p-eIF2α 表达与较短的总生存期相关（分别为 P= 0.048 和 P= 0.03）。多因素分析显示，高p-eIF2α（P=0.01）、切缘阳性（P=0.002）和淋巴结转移（P=0.01）是生存的独立预后因素。结论 PDAC中PERK和p-eIF2α的表达水平高于正常胰腺。高水平的 PERK 和 p-eIF2α 是 PDAC 患者生存期较短的预测因素，这表明 PERK 和 eIF2α 可能是 PDAC 中有希望的靶标。
ObjectivesEndoplasmic reticulum stress and subsequent phosphorylation of eukaryotic initiation factor 2α (eIF2α) by protein kinase R–like endoplasmic reticulum kinase (PERK) plays an important role in the development and chemoresistance of pancreatic ductal adenocarcinoma (PDAC). However, the expression and significance of phosphorylated eIF2α (p-eIF2α) and PERK in PDAC have not been examined.MethodsWe examined p-eIF2α and PERK expression in 84 PDAC and paired normal pancreas samples by immunohistochemistry and Western blotting and correlated the results with clinicopathologic parameters and survival.ResultsMean PERK H score was 140.8 in PDAC compared with 82.1 in normal pancreas (P< 0.001). High p-eIF2α expression was present in 56% of PDACs versus 7.6% of normal pancreases (P< 0.001). High PERK and p-eIF2α expression correlated with shorter overall survival (P= 0.048 and P= 0.03, respectively). By multivariate analysis, high p-eIF2α (P= 0.01), positive margin (P= 0.002), and lymph node metastasis (P= 0.01) were independent prognosticators for survival.ConclusionsThe expression levels of PERK and p-eIF2α are higher in PDAC than those in normal pancreas. High levels of PERK and p-eIF2α are predictors of shorter survival in PDAC patients, suggesting that PERK and eIF2α could be promising targets in PDAC.