Systemic Dyslipidemia Drives Pan-Cancer Prognosis via Epigenetic Remodeling: A Hybrid Pi-Score Analysis

Area of Science:

• Epigenetics
• Metabolic Disorders
• Oncology

Background:

• Dyslipidemia is a common metabolic disorder and a risk factor for cancer mortality.
• The epigenetic links between systemic lipid profiles and cancer aggressiveness are not well understood.

Purpose of the Study:

• To investigate the epigenetic landscape shared between lipid profiles and cancer prognosis.
• To identify specific lipid markers and epigenetic alterations associated with cancer aggressiveness.

Main Methods:

• Analyzed blood DNA methylation profiles from 2749 individuals (KoGES cohort).
• Integrated data with TCGA cancer types using a novel 'Hybrid Pi-score' algorithm.
• Examined associations between triglycerides, total cholesterol, HDL cholesterol, and cancer epigenetic data.

Main Results:

• Triglycerides showed a stronger epigenetic association with cancer prognosis than cholesterol markers, especially in metabolic cancers (LIHC, KIRC).
• Hypertriglyceridemia-associated methylation changes in healthy individuals mirrored those in high-mortality cancer groups.
• CPT1A was identified as a key epigenetic locus linking dyslipidemia to tumor progression.

Conclusions:

• Systemic dyslipidemia, particularly elevated triglycerides, drives oncogenic epigenetic remodeling.
• CPT1A may be a crucial target for mitigating lipid-driven cancer acceleration.
• Integrating lipid biomarkers into cancer risk stratification is recommended.