ArticleGeroScience2026
Subtype-specific sirtuin expression signatures link mitochondrial-epigenetic networks to breast cancer survival.
Article in GeroScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
2 citing papers in PubMed.
- Gut Microbiota-Targeted Nutrition for Healthy Aging: Mechanistic Roles of Polyphenols and Dietary Fiber in Geroscience.Nutrients · 2026Review
- Pathological triad of perioperative acute kidney injury: renal microcirculatory hypoxia, mitochondrial damage, and immuno-metabolic reprogramming.Frontiers in immunology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
Sirtuins (SIRT1-SIRT7) are NAD⁺-dependent regulators of mitochondrial metabolism, chromatin remodeling, and stress resilience pathways-processes that are central to both aging biology and breast cancer (BC) heterogeneity. We systematically evaluated their prognostic and transcriptional patterns across molecular subtypes of BC. We constructed an integrated BC dataset comprising gene expression and survival data containing tumors from 55 datasets. Prognostic associations with recurrence-free survival (RFS, n = 4384) were evaluated by univariate Cox and Kaplan-Meier analyses using best cutoffs with FDR control, first for individual sirtuins and then for multigene combinations. Differential expression across normal, tumor, and metastatic tissues, as well as pairwise coexpression (Spearman's ρ), was assessed using the TNMplot platform. Among individual genes, SIRT3 showed the most consistent association with improved RFS across PAM50 subtypes. Multigene signatures outperformed individual sirtuins and displayed clear subtype specificity. A three-gene panel (SIRT3+SIRT5+SIRT6) stratified risk in Luminal A (p = 8.1e-7), Luminal B (p = 6.6e-6), HER2-enriched (p = 1.0e-4), and Basal-like BC (p = 3.8e-5). In Basal-like tumors, the combination of SIRT3, SIRT6, and SIRT7 achieved the best performance (p = 2.6e-7). Top-performing panels were not simple aggregates of individually significant genes, indicating synergistic, context-dependent effects. Expression analyses revealed concordant downregulation of SIRT3 and SIRT5 in tumors, accompanied by consistent upregulation of SIRT7. Coexpression analysis revealed disease-specific rewiring: tumors exhibited a reinforced axis linking SIRT3/SIRT5/SIRT6/SIRT2, and attenuation of SIRT1 and SIRT4 coupling. Distinct integrated sirtuin scores thus capture subtype-specific metabolic/epigenetic states and provide robust RFS stratification across BC subtypes. These findings highlight sirtuins as integrators of longevity pathways and tumor metabolism, suggesting therapeutically exploitable vulnerabilities along NAD⁺-dependent regulatory axes.
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Registered trials
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