Cracking the Kinase Code: Urinary Biomarkers as Early Alarms for AAA Rupture-A Pilot Study.

Area of Science:

• Biochemistry
• Proteomics
• Vascular Biology

Background:

• Ruptured abdominal aortic aneurysm (RAAA) has a high mortality rate (nearly 90%).
• Clinical need exists for biomarkers to identify high-risk individuals.
• Non-invasive detection methods for abdominal aortic aneurysms (AAA) at risk of rupture are crucial.

Purpose of the Study:

• To identify potential alterations in the urine proteome for non-invasive detection of AAA.
• To discover urinary biomarkers for identifying AAA with a high risk of rupture.

Main Methods:

• Utilized multiplexed kinase inhibitor beads (MIBs) and quantitative mass spectrometry (MIB/MS) for urine proteome analysis.
• Employed iTRAQ labeling and LC-TEMPO MALDI-TOF/TOF for quantitative proteomic profiling.
• Validated findings using Western blot and analyzed data with R/Bioconductor and open-source bioinformatics tools.

Main Results:

• Quantitatively measured activity of over 130 kinases, identifying significant dysregulation in EPHB6, AXL, EPHB4, DDR1, EPHA2, and EPHB3.
• All identified significant proteins were tyrosine kinases, with a dominance of the Ephrin receptor type.
• Observed reduced expression of specific kinases was confirmed via Western blot.

Conclusions:

• Identified six dysregulated urinary tyrosine kinases as potential biomarkers for RAAA.
• These findings suggest a promising, non-invasive approach for early AAA detection and risk assessment.
• Further validation in larger prospective cohorts is necessary to confirm diagnostic utility and generalizability.