Comprehensive pan-cancer analysis reveals SIRT5 is a predictive biomarker for prognosis and immunotherapy response

Abstract

Abstract Background: SIRT5, a promising therapeutic target, modulates diverse cellular metabolic pathways. Its role in cancer remains elusive, necessitating a comprehensive pan-cancer analysis to elucidate its diagnostic, prognostic, and immunological significance. Methods: We conducted an extensive investigation into SIRT5's involvement in tumorigenesis, diagnosis, prognosis, metabolic pathways, the immune microenvironment, and therapeutic responses across multiple cancers. Chemical modifiers of SIRT5 expression were explored, along with the relationship between SIRT5 and drug sensitivity. Furthermore, in vitro and in vivo experiments assessed SIRT5's role in melanoma. Results: Differential expression of SIRT5 exhibited early diagnostic potential across various tumors, influenced by somatic cell copy number alterations and DNA methylation. SIRT5 expression correlated with clinical features and distinct metabolic, metastasis-related, and immune pathways. High SIRT5 levels predicted poor prognosis and impacted drug sensitivity. Additionally, SIRT5 expression correlated significantly with immune modulation, lymphocyte subpopulation infiltration, and immunotherapeutic response biomarkers. Varied SIRT5 expression was observed in immunotherapy cohorts. A range of chemicals affecting SIRT5 expression was identified. Notably, our findings underscore SIRT5 as a pivotal pathogenic factor promoting melanoma progression. Conclusion: Our study presents a comprehensive analysis of SIRT5 and its regulatory genes, highlighting its robust diagnostic and prognostic potential across diverse cancers. SIRT5 may remodel the tumor microenvironment and holds promise for guiding immunotherapy responses. This underscores the potential of SIRT5-based cancer therapies.