Omics profiling of OSA patients revealed a novel biomarker panel (two proteins and three metabolites) capable of identifying severe OSA with high accuracy, and identified glycolysis pathway activation, dyslipidaemia, foamy macrophage formation, platelet activation, and actin cytoskeleton dysregulation as molecular mechanisms linking OSA to cardiometabolic complications.
Key Findings
Results
A five-component biomarker panel distinguished severe OSA from controls with perfect accuracy and from nonsevere cases with good accuracy.
The panel comprised two proteins (ACTR2 and ENO1) and three metabolites (2-aminobicyclo[2.2.1]heptane-2-carboxylic acid, 1-O-[2r-hydroxy-hexadecyl]-sn-glycerol, and 1-pentadecene).
AUC for identifying S-OSA was 1.000.
AUC for distinguishing severe from nonsevere cases was 0.813.
An independent validation cohort confirmed the model, with AUC of 0.990 for S-OSA vs. controls and AUC of 0.729 for S-OSA vs. M-OSA.
Results
Proteomic and metabolic signatures significantly differed among severe OSA, mild/moderate OSA, and control groups.
142 plasma samples were analyzed: 50 controls (CON), 45 mild/moderate OSA (M-OSA), and 47 severe OSA (S-OSA) patients.
Both proteomic and metabolic profiles showed distinct separation across the three groups.
The study employed an omics approach integrating proteomics and metabolomics on plasma samples.
Results
Glycolysis pathway activation was identified as a characteristic molecular feature of OSA and may contribute to diabetes mellitus onset.
Glycolysis pathway activation was detected through omics profiling of OSA patient plasma.
The authors propose this pathway activation may mechanistically contribute to diabetes mellitus development in OSA patients.
This finding provides a molecular basis for the known clinical association between OSA and metabolic disorders.
Results
Dyslipidaemia, foamy macrophage formation, platelet activation, and actin cytoskeleton dysregulation were identified as collectively playing a key role in vascular damage in OSA patients.
These four processes were identified through omics profiling as molecular features distinguishing OSA patients.
The authors propose these mechanisms collectively contribute to atherosclerosis development in OSA patients.
ACTR2, one of the biomarker proteins, is associated with actin cytoskeleton regulation.
ENO1, the other biomarker protein, is a glycolytic enzyme, consistent with the identified glycolysis pathway activation.
Methods
The study design used separate discovery and validation cohorts to develop and test the biomarker panel.
A primary cohort of 142 plasma samples was used for biomarker discovery.
An independent cohort was used to validate the diagnostic model.
Validation AUCs were 0.990 for S-OSA vs. CON and 0.729 for S-OSA vs. M-OSA, indicating good but somewhat reduced performance compared to discovery.
What This Means
This research suggests that people with obstructive sleep apnoea (OSA) — a condition where breathing repeatedly stops during sleep — have distinct patterns of proteins and small molecules in their blood compared to people without OSA, and these patterns differ based on how severe the OSA is. Scientists analyzed blood plasma from 142 people (50 without OSA, 45 with mild-to-moderate OSA, and 47 with severe OSA) and identified a combination of two proteins (ACTR2 and ENO1) and three metabolites that could identify severe OSA with near-perfect accuracy. When tested in a separate, independent group of patients, the same panel still performed well, suggesting these markers could potentially be useful diagnostic tools.
Beyond diagnosis, the study uncovered biological pathways that may explain why OSA patients are at higher risk of developing serious health problems. The researchers found evidence that OSA activates glycolysis (a process cells use to break down sugar for energy), which may set the stage for diabetes. They also found signs of abnormal fat metabolism, the formation of 'foamy' immune cells linked to artery disease, increased platelet activity (which promotes blood clotting), and disruptions in cell structure — all of which could damage blood vessels and lead to atherosclerosis (hardening of the arteries).
This research matters because it moves beyond simply describing that OSA is associated with heart and metabolic diseases, and instead points to specific molecular mechanisms that may drive these complications. If confirmed in larger studies, these findings could lead to better blood tests for diagnosing severe OSA and might eventually help identify patients most at risk of developing diabetes or cardiovascular disease, potentially enabling earlier or more targeted interventions.
Zhao Z, Kang H, Li X, Wang Y, Wu X, Liu J, et al.. (2026). Omics Profiling of Patients with Obstructive Sleep Apnoea Reveals Risks of Diabetes Mellitus and Cardiovascular Diseases.. Journal of proteome research. https://doi.org/10.1021/acs.jproteome.5c00919