• Regent Lee, Ismail Cassimjee, Honglei Huang, Pierfrancesco Lapolla, Elisha Ngetich, Anirudh Chandrashekar, Philip Charles, Benedikt Kessler, Roman Fischer, and Ashok Handa.
• Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
• Ann. Surg. 2022 Jun 1; 275 (6): 1206-1211.

ObjectiveDiscovery of novel biomarkers for AAA growth prediction.BackgroundNovel biomarker of AAA growth is a recognized priority in research. Our prior work implicated intraluminal thrombus (ILT) in AAAs to be a potential source of systemic mediators during AAA progression. Here we applied a mass spectrometry proteomics pipeline to discover novel biomarkers for AAA growth prediction.MethodsPatients were prospectively recruited. Plasma samples were collected at baseline (n = 62). AAA growth was recorded at 12 months. In Experiment 1, plasma samples from the fastest and slowest growth patients (n = 10 each) were compared. In Experiment 2, plasma samples were collected before and at 10-12 weeks after surgery (n = 29). In Experiment 3, paired ILT and omental biopsies were collected intra-operatively during open surgical repair (n = 3). In Experiment 4, tissue secretome was obtained from ex-vivo culture of these paired tissue samples. Samples were subjected to a liquid chromatography tandem mass spectrometry workflow to discover novel biomarkers.ResultsWe discovered 3 proteins that are: (i) present in ILT; (ii) released by ILT; (iii) reduced in circulation after AAA surgery; (iv) differs between fast and slow growth AAAs. One of these is Attractin. Plasma Attractin correlates significantly with future AAA growth (Spearman r = 0.35, P < 0.005). Using Attractin and AAA diameter as input variables, the area under receiver operating characteristics for predicting no growth and fast growth or AAA at 12 months is 85% and 76%, respectively.ConclusionWe show that ILT of AAAs releases mediators during the natural history of AAA growth. These are novel biomarkers for AAA growth prediction in humans.Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.

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