Differential expression of the sirtuin family in renal cell carcinoma: Aspects of carcinogenesis and prognostic significance
Differential expression of the sirtuin family in renal cell carcinoma: Aspects of carcinogenesis and prognostic significance
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DOI：
10.1016/j.urolonc.2017.08.016
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发表时间：
2017-12-01
影响因子：
2.7
通讯作者：
Hwa, Jeong Seok
中科院分区：
文献类型：
--
作者：
Jeh, Seong Uk;Park, Jung Je;Hwa, Jeong Seok
目的：Sirtuins（1-7）是进化上保守的nad依赖性去乙酰化酶，在癌变过程中发挥重要作用。然而，它们在肾细胞癌（RCC）中的作用尚不清楚。本研究的目的是研究sirt在肾癌发生和预后中的作用。材料与方法：对2004年1月至2010年12月行肾肿块切除手术的102例患者的石蜡包埋标本进行分析。通过免疫组化染色比较RCC与邻近正常肾脏组织的SIRT表达，分别采用Kaplan-Meier log-rank检验和单因素和多因素Cox回归分析生存差异和癌症特异性生存。结果：SIRT1、SIRT3和SIRT6在RCC中的表达明显低于正常组织（P = 0.001、P = 0.006和P = 0.033），而其他SIRT蛋白在两种组织中的表达无显著差异。在调整年龄、T分期、Fuhrman分级、Karnofsky性能状态和远处转移后，SIRT3表达与较长的癌症特异性生存期（HR = 0.133, P = 0.047）显著相关。Kaplan-Meier分析显示，sirt3高表达患者的生存期相对于sirt3低表达患者（P = 0.046， log-rank检验）。结论：我们的研究结果提供了初步证据，表明SIRT1、SIRT3和SIRT6在RCC中发挥抑癌作用。特别是SIRT3似乎对透明细胞RCC患者的生存有有利的影响。(C) 2017爱思唯尔公司版权所有。
Objectives: Sirtuins (1-7) are evolutionarily conserved NAD-dependent deacetylases that play an important role in carcinogenesis. However, their role in renal cell carcinoma (RCC) remains unclear. The objective of the present study was to examine the role of SIRTs in RCC carcinogenesis and prognosis.Materials and methods: Paraffin-embedded specimens from 102 patients who underwent extirpative renal surgeries for renal masses between January 2004 and December 2010 were examined. SIRT expression was compared between RCC and adjacent normal kidney tissues by immunohistochemical staining Survival differences and cancer-specific survival were analyzed with the Kaplan-Meier log-rank test and univariate and multivariate Cox regression analyses, respectively.Results: SIRT1, SIRT3, and SIRT6 expression was significantly lower in RCC than in normal tissues (P = 0.001, P = 0.006, and P = 0.033, respectively), whereas the expression of other SIRT proteins did not differ significantly between the 2 tissues. SIRT3 expression was significantly associated with longer cancer-specific survival (HR = 0.133, P = 0.047), after adjusting for age, T stage, Fuhrman grade, Karnofsky performance status, and distant metastases. Kaplan-Meier analysis showed that patients with high-SIRT3 expression had relatively better survival than those with low-SIRT3 expression (P = 0.046, log-rank test).Conclusions: Our results provide preliminary evidence suggesting that SIRT1, SIRT3, and SIRT6 function as tumor suppressors in RCC. In particular, SIRT3 seems to have a favorable influence on the survival of patients with clear cell RCC. (C) 2017 Elsevier Inc. All rights reserved.