ArticleJACC. CardioOncology2026
Cardiovascular-Kidney-Metabolic Syndrome Staging and Cancer Risk: Insights From Proteomic and Metabolomic Mediators.
Article in JACC. CardioOncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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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Who cites it
1 citing paper in PubMed.
- The Cardiometabolic-to-Cancer Axis: Molecular Insights From Cardio-Kidney-Metabolic Syndrome Staging.JACC. CardioOncology · 2026Article
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCardiovascular-kidney-metabolic (CKM) syndrome is an emerging integrative framework and a critical determinant of overall disease risk; however, its relationship with cancer risk and underlying mechanisms remains poorly understood.
objectivesThis study sought to investigate the association between CKM staging and incident cancer and elucidate mediators underlying this association, thereby uncovering pathways and potential targets for risk mitigation based on multiomics analysis.
methodsUK Biobank participants were categorized into CKM stages 0 to 4 according to the American Heart Association staging framework based on International Classification of Diseases, 10th Revision codes. Cox regression was conducted to evaluate associations between CKM staging and overall cancer incidence. Proteomic and metabolomic mediators linking adjacent stages and cancer were identified using Cox regression, logistic regression, and mediation analysis and underwent Gene Ontology enrichment and interaction network analyses.
resultsOverall cancer risk increased stepwise from CKM stages 1 to 3, with slight attenuation but persistent elevation in stage 4. Stage-specific mediators and mechanisms were identified: leukocyte/lymphocyte activation and cell-cell adhesion in stage 1; T cell-related immunity and emerging immune tolerance induction in stage 2; emerging natural killer (NK) cell tolerance induction and respiratory burst involved in the inflammatory response in stage 3; and dominant NK cell tolerance induction and tissue-resident chronic pathology in stage 4. Dominant metabolomic mediation evolved from high-density lipoproteins (HDLs) and triglyceride-rich lipoproteins (TRLs) to low-density lipoproteins (LDLs). Protein-metabolite interaction networks revealed distinct profiles for each stage, including angiopoietin-like protein 1/HDL and asialoglycoprotein receptor 1/TRL interactions in early stages and phospholipid transfer protein/HDL, apolipoprotein M/LDL, and fibroblast growth factor-binding protein 1/intermediate-density lipoprotein/LDL correlations in advanced stages.
conclusionsCKM staging is associated with incremental cancer risk and stage-specific immune-metabolic pathways, highlighting potential prevention targets.
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