Integrated proteomics identified CHRDL1, OGN, and CCL18 as promising plasma biomarkers for AAA detection, with a combined three-protein model demonstrating strong diagnostic performance with an AUC of 0.890.
Key Findings
Results
DIA mass spectrometry proteomics identified 111 differentially abundant proteins in plasma samples from AAA patients compared to healthy controls.
Plasma samples from 22 patients with AAA and 22 healthy controls were analyzed
Data-independent acquisition (DIA) mass spectrometry was the analytical method used
Differentially expressed proteins were subjected to Gene Ontology enrichment, KEGG pathway analysis, protein-protein interaction, and weighted gene coexpression network analyses
Enriched pathways included mitochondrial respiration, oxidative stress, inflammation, extracellular matrix remodeling, and proteostasis
Results
Plasma CHRDL1 levels were significantly reduced in patients with AAA compared to controls.
CHRDL1 reduction was identified in the discovery cohort (22 AAA patients, 22 controls) via DIA proteomics
The finding was consistently confirmed in an independent validation cohort of 93 AAA patients and 83 non-AAA controls
Validation was performed using enzyme-linked immunosorbent assay (ELISA)
CHRDL1 was selected as a candidate based on differential abundance, diagnostic performance, and biological relevance
Results
Plasma OGN levels were significantly elevated in patients with AAA compared to controls.
OGN elevation was identified in the discovery cohort via DIA proteomics
The finding was consistently confirmed in the independent validation cohort (93 AAA patients, 83 non-AAA controls)
Validation was performed using ELISA
OGN was selected based on differential abundance, diagnostic performance, and biological relevance
Results
Plasma CCL18 levels were significantly elevated in patients with AAA compared to controls.
CCL18 elevation was identified in the discovery cohort via DIA proteomics
The finding was consistently confirmed in the independent validation cohort (93 AAA patients, 83 non-AAA controls)
Validation was performed using ELISA
CCL18 was selected based on differential abundance, diagnostic performance, and biological relevance
Results
A combined three-protein model using CHRDL1, OGN, and CCL18 demonstrated strong diagnostic performance for AAA detection.
The combined model achieved an area under the receiver operating characteristic curve (AUC) of 0.890
The model incorporated all three candidate biomarkers: CHRDL1, OGN, and CCL18
The validation cohort comprised 93 patients with AAA and 83 non-AAA controls
Individual biomarker performance was not specified in the abstract but candidates were selected based on diagnostic performance criteria
Results
Proteomic analysis highlighted mitochondrial dysfunction, chronic inflammation, ECM remodeling, and dysregulated proteostasis as key molecular features of AAA.
Pathways enriched among the 111 differentially abundant proteins included mitochondrial respiration, oxidative stress, inflammation, extracellular matrix remodeling, and proteostasis
Bioinformatic analyses included Gene Ontology enrichment, KEGG pathway analysis, protein-protein interaction networks, and weighted gene coexpression network analyses
These molecular features were identified from the DIA proteomics discovery phase
Authors describe these as 'key molecular features of AAA'
What This Means
Abdominal aortic aneurysm (AAA) is a dangerous condition where the main blood vessel in the abdomen becomes dangerously enlarged. It is often 'silent' with no symptoms until it ruptures, which can be fatal. Currently, there are no reliable blood tests to detect it, so doctors rely on ultrasound screening. This study sought to find proteins in the blood that could serve as biomarkers — measurable signals — to help identify AAA non-invasively. Researchers analyzed blood plasma from AAA patients and healthy individuals using an advanced protein-detection technology called data-independent acquisition mass spectrometry, finding 111 proteins that were present at different levels between the two groups. Three proteins stood out as particularly promising: CHRDL1 (which was lower in AAA patients), and OGN and CCL18 (which were both higher in AAA patients). These findings were then confirmed in a separate, larger group of 93 AAA patients and 83 controls using a standard laboratory test called ELISA.
When all three proteins were combined into a single diagnostic model, it achieved an AUC (area under the curve) of 0.890 — a measure of diagnostic accuracy where 1.0 is perfect and 0.5 is no better than chance. This suggests the combined test could reliably distinguish AAA patients from healthy individuals. The study also revealed that AAA is associated with molecular disruptions in energy production (mitochondrial dysfunction), inflammation, breakdown of the structural scaffold around cells (extracellular matrix remodeling), and problems with protein quality control (proteostasis).
This research suggests that measuring CHRDL1, OGN, and CCL18 together in a blood sample could potentially offer a new, minimally invasive way to screen for or diagnose AAA. This could be particularly valuable for detecting the disease before it reaches a dangerous stage. Further studies in larger and more diverse populations would be needed to confirm whether such a blood test could be reliably used in clinical practice.
Ma H, Gao J, Cai Y, Xie Z, Wu L, Xiang W, et al.. (2026). Identification and Validation of Plasma Protein Biomarkers for Abdominal Aortic Aneurysm Using Integrated Proteomics.. International journal of molecular sciences. https://doi.org/10.3390/ijms27167312