Identification of Shared Signature Genes and Immune Microenvironment Subtypes for Heart Failure and Chronic Kidney...

Area of Science:

• Cardiovascular Medicine
• Nephrology
• Molecular Biology

Background:

• Heart failure (HF) and chronic kidney disease (CKD) exhibit a complex interrelationship.
• Understanding the molecular mechanisms of this organ-to-organ interplay is crucial.
• Identifying sensitive and specific biomarkers for both conditions is a significant clinical need.

Purpose of the Study:

• To clarify the molecular mechanisms underlying the interplay between HF and CKD.
• To identify sensitive and specific biomarkers for the simultaneous diagnosis of HF and CKD.
• To explore molecular subtypes and immune characteristics of co-existing HF and CKD.

Main Methods:

• Differential gene expression analysis of HF and CKD microarray datasets.
• Machine learning for biomarker identification and validation using ROC curves and RT-PCR.
• Consensus clustering for molecular subtyping and ssGSEA for immune cell infiltration analysis.

Main Results:

• Identified 33 crosstalk genes linked to inflammatory, immune, and metabolic pathways.
• Five hub genes (PHLDA1, ATP1A1, IFIT2, HLTF, MPP3) selected as optimal diagnostic biomarkers.
• Discovered distinct immune and metabolic subtypes of HF and CKD, with significant immune dysregulation.

Conclusions:

• Five identified crosstalk genes show potential as diagnostic biomarkers for HF and CKD.
• Metabolite disorders and subsequent immune cell activation are key to the common pathogenesis of HF and CKD.
• An ImmuneScore model accurately predicted molecular subtypes, aiding risk stratification.