Tan Ying, Li Bijuan, Peng Fang, Gong Guanghui, Li Ning
Department of Blood Transfusion, Xiangya Hospital, Central South University, Changsha, China.
NHC Key Laboratory of Cancer Proteomics, Xiangya Hospital, Central South University, Changsha, China.
Front Oncol. 2020 Feb 25;10:218. doi: 10.3389/fonc.2020.00218. eCollection 2020.
Sirtuins, class III histone deacetylases, are involved in multiple biological processes in cancer initiation and progression. However, the diverse expression patterns and prognostic values of sirtuins in cancers have yet to be elucidated. In this study, we first evaluated the expression and prognostic values of sirtuins in multiple cancer cohorts using publicly available TCGA pan-cancer datasets. Pan-cancer survival analysis indicated that 6 out of 7 sirtuin family members were significant associated with prognosis of clear cell renal cell carcinoma (KIRC) patients. SIRT1, SIRT3, SIRT4, and SIRT5 were associated with favorable prognosis of KIRC patients, while SIRT6 and SIRT7 were associated with unfavorable prognosis. The expression levels of SIRT4 and SIRT5 in KIRC tissues were lower than that in normal tissues, while SIRT6 and SIRT7 were higher in KIRC tissues. The expression levels of SIRT1, SIRT3, SIRT5, SIRT6, and SIRT7 were significantly correlated with tumor stage and histological grade. DNA methylation may contribute to the dysregulation of sirtuins. Finally, GSEA was conducted to predict the potential functions of sirtuins in KIRC. Our results may provide novel insights for the development of sirtuins-based cancer therapy in KIRC.
沉默调节蛋白（Sirtuins）是III类组蛋白去乙酰化酶，参与癌症发生和发展的多个生物学过程。然而，沉默调节蛋白在癌症中的多种表达模式和预后价值尚未阐明。在本研究中，我们首先使用公开可用的TCGA泛癌数据集评估了多个癌症队列中沉默调节蛋白的表达和预后价值。泛癌生存分析表明，7个沉默调节蛋白家族成员中的6个与肾透明细胞癌（KIRC）患者的预后显著相关。SIRT1、SIRT3、SIRT4和SIRT5与KIRC患者的良好预后相关，而SIRT6和SIRT7与不良预后相关。KIRC组织中SIRT4和SIRT5的表达水平低于正常组织，而SIRT6和SIRT7在KIRC组织中较高。SIRT1、SIRT3、SIRT5、SIRT6和SIRT7的表达水平与肿瘤分期和组织学分级显著相关。DNA甲基化可能导致沉默调节蛋白的失调。最后，进行基因集富集分析（GSEA）以预测沉默调节蛋白在KIRC中的潜在功能。我们的结果可能为KIRC中基于沉默调节蛋白的癌症治疗发展提供新的见解。
