An integrated bioinformatics and multi-omics investigation of the sirtuin family to identify their prognostic importance in human cancers

BackgroundIn recent years, the significance of sirtuins in cancer biology has become increasingly evident, but their molecular mechanisms and prognostic impacts remain elusive.ObjectiveThe present study aimed to investigate the differential expression of the sirtuin gene family across cancers and to evaluate their prognostic value.MethodsWe used various bioinformatics databases and methodologies, including Oncomine, GEPIA, OncoDB, cBioPortal, R2 Kaplan-Meier Scanner, STRING, etc., to determine the expression pattern of the sirtuin family genes, along with their mutations and prognostic values in human cancers.ResultsIn the current study, <i>SIRT1</i>, <i>SIRT2</i>, <i>SIRT4</i>, and <i>SIRT5</i> were downregulated in lymphoma, whereas <i>SIRT6</i> and <i>SIRT7</i> were overexpressed. In breast cancer, <i>SIRT3</i>, <i>SIRT5</i>, and <i>SIRT7</i> were overexpressed, and in terms of kidney cancer, higher expression of <i>SIRT2</i>, <i>SIRT3</i>, and <i>SIRT5</i> was observed. In contrast, for leukemia, bladder, and brain cancers, most sirtuin family members showed reduced expression. We found that most mutations occurred in uterine cancer, chRCC (chromophobe renal cell carcinoma), DLBCL (diffuse large B-cell lymphoma), melanoma, pRCC (papillary renal cell carcinoma), and esophageal cancer. Moreover, we identified the relevant functional proteins through protein-protein interaction analysis to evaluate copy number alterations (CNAs) in sirtuins. The most frequent alterations were amplifications and deep deletions. Survival analysis demonstrated that <i>SIRT1</i> and <i>SIRT2</i> overexpression correlated with improved overall survival in low-grade glioma but predicted poorer outcomes in ovarian cancer. Downregulation of <i>SIRT1</i>, <i>SIRT3</i>, and <i>SIRT5</i> was associated with better prognosis in DLBCL, while <i>SIRT3</i> and <i>SIRT4</i> upregulation predicted favorable survival in testicular germ cell tumors. <i>SIRT6</i> overexpression was linked to favorable prognosis in esophageal carcinoma and sarcoma, while unfavorable outcomes were observed in hepatocellular carcinoma and cholangiocarcinoma. <i>SIRT7</i> upregulation was significantly associated with reduced survival in esophageal, liver, and uterine cancers, but surprisingly correlated with improved outcomes in urothelial carcinoma and cervical squamous cell carcinoma.ConclusionsTogether, this multi-omics analysis reveals the correlation and prognostic values of sirtuins across multiple types of human cancers and suggests that sirtuins may serve as promising biomarkers for different cancers.