Prognostic value of sirtuin family members and experimental verification identify SIRT5 as diagnostic biomarkers in clear cell renal cell carcinoma

PeerJ

article

Lu-Shan Peng¹  Sai-Li Duan²  Run-Qi Li³  Zi-Yuan Bai⁴  Chun-Lin Ou¹  Jun-Pu Wang¹ 

[1] Department of Pathology, Xiangya Hospital;Department of General Surgery, Xiangya Hospital;Department of Pathology, School of Basic Medicine, Central South University;Department of Pathology, First Affiliated Hospital of Kunming Medical University;National Clinical Research Center for Geriatric Disorders, Xiangya Hospital;Key Laboratory of Hunan Province in Neurodegenerative Disorders, Xiangya Hospital

关键词: Bioinformatics;    Immune cell infiltration;    Renal cell clear cell carcinoma;    Prognosis;    Sirtuin;   

DOI  :  10.7717/peerj.15154

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundThe 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.MethodsWe 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.ResultsThe 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.ConclusionSIRT5 may be a prognostic marker and a novel strategy for the treatment of ccRCC.

【 授权许可】

CC BY