Sirtuin 家族成员的预后价值及实验验证将 SIRT5 鉴定为透明细胞肾细胞癌的诊断生物标志物。
Prognostic value of sirtuin family members and experimental verification identify SIRT5 as diagnostic biomarkers in clear cell renal cell carcinoma.
机构信息
Department of Pathology, Xiangya Hospital, Changsha, Hunan, China.
Department of General Surgery, Xiangya Hospital, Changsha, Hunan, China.
出版信息
PeerJ. 2023 Apr 19;11:e15154. doi: 10.7717/peerj.15154. eCollection 2023.
BACKGROUND
The sirtuins (SIRTs) family is a nicotinamide adenine dinucleotide (NAD+) family of dependent deacetylases, which includes SIRT1-7. This family is related to the development and progression of various tumors. However, a comprehensive analysis of the role of SIRTs in clear cell renal cell carcinoma (ccRCC) is still lacking, and there are few reports on the inhibitory role of SIRT5 in ccRCC.
METHODS
We used immunohistochemical analysis, and several bioinformatic databases to perform an integrated analysis of the expression and prognostic value of SIRT5 and other SIRT family members in ccRCC along with the associated immune cell infiltration. These databases include TIMER, THPA, cell culture, UALCAN, cBioPortal, WebGestalt, Metascape, DiseaseMeth, STRING database, and Cytoscape.
RESULTS
The protein expression of SIRT1, 2, 3, 6, and 7 were upregulated in ccRCC for the Human Protein Atlas database, whereas the expression of SIRT4 and SIRT5 was decreased. The expression based on tumor stage, and grade followed a similar trend. Kaplan-Meier analysis showed that high SIRT4 and SIRT5 expression was positively related to better overall survival (OS), whereas SIRT6 and SIRT7 expression was positively related to worse OS. Further, high SIRT3 expression was related to worse relapse-free survival (RFS), whereas high SIRT5 expression was related to better RFS. To explore the mechanism underlying the function of SIRTs in ccRCC, we also used several databases to perform the functional enrichment analysis and explore the relationship between infiltrating immune cells and seven SIRT family members in ccRCC. The results showed that several SIRT family members, and particularly SIRT5, are correlated with the infiltration of some important immune cells. The protein expression of SIRT5 was significantly lower in tumor tissue compared to normal tissue and was negatively related to the age of the patient ccRCC individual tumor stages, and grades. In human ccRCC samples, strong IHC staining expression of SIRT5 was displayed in adjacent normal tissue than in tumor tissues.
CONCLUSION
SIRT5 may be a prognostic marker and a novel strategy for the treatment of ccRCC.
背景
沉默调节蛋白（SIRTs）家族是烟酰胺腺嘌呤二核苷酸（NAD+）依赖性去乙酰化酶家族，包括 SIRT1-7。该家族与各种肿瘤的发生和发展有关。然而，SIRTs 在透明细胞肾细胞癌（ccRCC）中的作用仍缺乏全面分析，并且关于 SIRT5 在 ccRCC 中的抑制作用的报道很少。
方法
我们使用免疫组织化学分析以及几个生物信息学数据库，对 SIRT5 和其他 SIRT 家族成员在 ccRCC 中的表达和预后价值以及相关免疫细胞浸润进行综合分析。这些数据库包括 TIMER、THPA、细胞培养、UALCAN、cBioPortal、WebGestalt、Metascape、DiseaseMeth、STRING 数据库和 Cytoscape。
结果
基于人类蛋白质图谱数据库，SIRT1、2、3、6 和 7 的蛋白表达在 ccRCC 中上调，而 SIRT4 和 SIRT5 的表达下调。基于肿瘤分期和分级的表达也呈现出相似的趋势。Kaplan-Meier 分析表明，高 SIRT4 和 SIRT5 表达与更好的总生存期（OS）相关，而 SIRT6 和 SIRT7 表达与更差的 OS 相关。此外，高 SIRT3 表达与更差的无复发生存率（RFS）相关，而高 SIRT5 表达与更好的 RFS 相关。为了探讨 SIRTs 在 ccRCC 中的功能机制，我们还使用几个数据库进行功能富集分析，并探讨 ccRCC 中七种 SIRT 家族成员与浸润免疫细胞的关系。结果表明，几个 SIRT 家族成员，特别是 SIRT5，与一些重要免疫细胞的浸润有关。SIRT5 的蛋白表达在肿瘤组织中明显低于正常组织，与患者的年龄、ccRCC 个体肿瘤分期和分级呈负相关。在人 ccRCC 样本中，SIRT5 的强免疫组化染色表达在相邻正常组织中比在肿瘤组织中更为明显。
结论
SIRT5 可能是 ccRCC 的预后标志物和治疗新策略。
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