Nuclear expression of Smad proteins and its prognostic significance in clear cell renal cell carcinoma
Nuclear expression of Smad proteins and its prognostic significance in clear cell renal cell carcinoma
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DOI：
10.1016/j.humpath.2013.03.009
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发表时间：
2013-10-01
期刊：
影响因子：
3.3
通讯作者：
Moon, Kyung Chul
中科院分区：
文献类型：
--
作者：
Park, Jeong Hwan;Lee, Cheol;Moon, Kyung Chul
Smad2、Smad3和Smad4是与肿瘤发生相关的转化生长因子信号通路的组成部分。这些蛋白的表达与许多癌症的肿瘤进展和预后有关。本研究旨在评估Smad2、Smad3和Smad4在透明细胞肾细胞癌中的核表达，并评估其表达模式的临床意义和预后价值。应用免疫组织化学方法对637例透明细胞肾细胞癌中Smads的核表达水平进行了评价。为了确定Smad在透明细胞肾细胞癌中表达的统计学意义，根据核染色程度将每个病例分为低表达组和高表达组。Smad3和Smad4的核表达与患者年龄、核分级、肿瘤大小、pTNM分期呈负相关。Smad3-low和Smad4-low组的癌症特异性和无进展生存时间显著缩短。此外，多变量分析显示Smad3和Smad4都是无进展生存的独立预测因子（P = 0.008和P = 0.022）。然而，Smad2的表达与临床病理参数和患者的生存无关。这些结果提示Smad3和Smad4的核表达与透明细胞肾细胞癌患者的预后有关，可能作为透明细胞肾细胞癌患者新的预后标志物。(C) 2013爱思唯尔公司版权所有。
Smad2, Smad3, and Smad4 are components of the transforming growth factor signaling pathway associated with tumorigenesis. The expression of these proteins is associated with tumor progression and prognosis of many cancers. This study aimed to evaluate the nuclear expression of Smad2, Smad3, and Smad4 in clear cell renal cell carcinoma and to assess the clinical significance and prognostic value of their expression patterns. The nuclear expression levels of Smads were evaluated in 637 cases of clear cell renal cell carcinomas using immunohistochemistry. To determine the statistical significance of Smad expression in clear cell renal cell carcinoma, each of the cases were divided into 2 groups (low and high expression groups) according to the extent of nuclear staining. Nuclear expressions of Smad3 and Smad4 were inversely correlated with the patient's age, the nuclear grade, the tumor size, and the pTNM stage. The Smad3-low and Smad4-low groups showed significantly shorter cancer-specific and progression-free survival times. Furthermore, multivariate analysis showed that both Smad3 and Smad4 were independent predictors for progression-free survival (P = .008 and P = .022, respectively). However, Smad2 expression was not related to clinicopathologic parameters and patients' survival. These results suggest that nuclear expressions of Smad3 and Smad4 were related to prognosis of clear cell renal cell carcinoma patients and may serve as novel prognostic markers in clear cell renal cell carcinoma patients. (C) 2013 Elsevier Inc. All rights reserved.