The opposite prognostic significance of nuclear and cytoplasmic p21 expression in resectable gastric cancer patients
The opposite prognostic significance of nuclear and cytoplasmic p21 expression in resectable gastric cancer patients
复制标题
可切除胃癌患者核和细胞质p21表达的相反预后意义
DOI：
10.1007/s00535-013-0900-4
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发表时间：
2014-11-01
影响因子：
6.3
通讯作者：
Zhou, Jianwei
中科院分区：
文献类型：
--
作者：
Huang, Yefei;Wang, Weimin;Zhou, Jianwei
背景蛋白p21Cip1/Waf1是一种细胞周期蛋白依赖性的激酶抑制因子，在细胞周期停滞、衰老和细胞凋亡中发挥重要作用。有趣的是，细胞核和细胞质的p21在细胞中执行各种功能。本研究旨在探讨亚细胞p21在胃癌(GC)中的表达对预后的影响。方法采用免疫组织化学方法，在训练队列中用组织芯片检测亚细胞p21的表达，然后进入第二个测试队列，最后进入验证队列。评估亚细胞p21表达状态对预后和预测作用。结果与癌旁组织相比，癌组织中胞核和胞浆p21蛋白表达水平分别显著降低和升高。P21胞核低表达或胞浆p21高表达与患者总生存期(OS)缩短及临床病理特征显著相关。多因素回归分析显示，p21胞核低表达和胞浆高表达分别是OS的独立阴性标志物。结论细胞核和胞浆p21蛋白的表达在可切除胃癌中是一种新的候选预后标志物，它们在细胞迁移和侵袭中发挥着明显的作用。
BackgroundProtein p21Cip1/Waf1is a cyclin-dependent kinase inhibitor, which plays important roles in cell cycle arrest, senescence, and apoptosis. Interestingly, the nuclear and cytoplasmic p21 executes various functions in the cell. In this study, we investigated the prognostic impact of subcellular p21 expression in gastric cancer (GC).MethodsExpressions of subcellular p21 was assessed by immunohistochemistry using a tissue microarray in a training cohort and it went into a second testing cohort and finally to a validating cohort. Prognostic and predictive role of subcellular p21 expression status was evaluated. We also studied the roles of subcellular p21 in GC cell migration and invasion.ResultsNuclear and cytoplasmic p21 protein levels were significantly reduced and increased in GC lesions compared with adjacent non-cancerous tissues, respectively. Low nuclear p21 or high cytoplasmic p21 expression significantly correlated with shorter overall survival (OS), as well as with clinicopathologic characteristics in patients. Multivariate regression analysis showed that low nuclear and high cytoplasmic p21 expression, separately and together, were independent negative markers of OS. Finally, we found that nuclear p21 inhibits but cytoplasmic p21 promotes cell migration and invasion abilities.ConclusionsThese findings suggest that nuclear and cytoplasmic p21 protein expression in tumor are novel candidate prognostic markers in resectable human gastric carcinoma, and they exert distinct roles in cell migration and invasion.