Targeted proteomics and metabolomics for biomarker discovery in abdominal aortic aneurysm and post-EVAR sac volume
Clinica Chimica Acta, 2024
Vanmaele A., Bouwens E., Hoeks S., Kindt A., Lamont L., Fioole B., Moelker A., ten Raa S., Hussain B., Oliveira-Pinto J., Ijpma A., van Lier F., Akkerhuis K., Majoor-Krakauer D., Hankemeier T., de Rijke Y., Verhagen H., Boersma E., Kardys I.
Disease area | Application area | Sample type | Products |
---|---|---|---|
CVD | Patient Stratification | Plasma | Olink Target 96 |
Abstract
Background and aims
Abdominal aortic aneurysm (AAA) patients undergo uniform surveillance programs both leading up to, and following surgery. Circulating biomarkers could play a pivotal role in individualizing surveillance. We applied a multi-omics approach to identify relevant biomarkers and gain pathophysiological insights.
Materials and methods
In this cross-sectional study, 108 AAA patients and 200 post-endovascular aneurysm repair (post-EVAR) patients were separately investigated. We performed partial least squares regression and ingenuity pathway analysis on circulating concentrations of 96 proteins (92 Olink Cardiovascular-III panel, 4 ELISA-assays) and 199 metabolites (measured by LC-TQMS), and their associations with CT-based AAA/sac volume.
Results
The median (25th-75th percentile) maximal diameter was 50.0 mm (46.0, 53.0) in the AAA group, and 55.4 mm (45.0, 64.2) in the post-EVAR group. Correcting for clinical characteristics in AAA patients, the aneurysm volume Z-score differed 0.068 (95 %CI: (0.042, 0.093)), 0.066 (0.047, 0.085) and −0.051 (-0.064, -0.038) per Z-score valine, leucine and uPA, respectively. After correcting for clinical characteristics and orthogonalization in the post-EVAR group, the sac volume Z-score differed 0.049 (0.034, 0.063) per Z-score TIMP-4, −0.050 (-0.064, -0.037) per Z-score LDL-receptor, −0.051 (-0.062, -0.040) per Z-score 1-OG/2-OG and −0.056 (-0.066, -0.045) per Z-score 1-LG/2-LG.
Conclusions
The branched-chain amino acids and uPA were related to AAA volume. For post-EVAR patients, LDL-receptor, monoacylglycerols and TIMP-4 are potential biomarkers for sac volume. Additionally, distinct markers for sac change were identified.