Urinary biomarkers can diagnose and monitor pathophysiologic conditions in the central nervous system (CNS). However, focus is often on single diseases, with limited data on discriminatory capability of this approach in a general setting. Lately, we have demonstrated that different classes of CNS disease exhibit distinct biomarker patterns, evidence of disease-specific “fingerprinting.” In one of our latest studies, urine from 218 patients with pathology-confirmed tumors or cerebrovascular disease, controls (n = 33) were collected. ELISA and/or bead-based multiplexing quantified levels of 21 putative urinary biomarkers. Analysis identified biomarkers capable of distinguishing each disease from controls and other diseases. Mann–Whitney U tests identified biomarkers with differential expression between disease types and controls (P ≤ 0.001). Subsequent receiver-operating characteristic (ROC) analyses revealed distinguishing biomarkers with high sensitivity and specificity. Areas under the curve (AUCs) ranged 0.8563–1.000 (P values ≤ 0.0003), sensitivities ranged 80.00–100.00%, and specificities ranged 80.95–100.00%. These data demonstrate proof-of-principle evidence that disease-specific urinary biomarker signatures exist. In contrast to non-specific responses to ischemia or injury, these results suggest that urinary biomarkers accurately reflect unique biological processes distinct to different diseases. This work can be used to generate disease-specific panels for enhancing diagnosis, assisting less-invasive follow-up and herald utility by revealing putative disease-specific therapeutic targets.
We are currently have performed a high throughput screen to identify novel biomarkers in Cerebral Cavernous Malformations and Moyamoya disease. Updates about these projects are under consideration for publication.
Selected Publication:
Duggins-Warf M, Ghalali A, Sesen J, Martinez T, Fehnel P K, Pineda S, Zurakowski D, Smith E R. Disease Specific Urinary Biomarkers in the Central Nervous System. Sci Rep. 2023 Nov 7;13(1):19244.
Ashok K, Martinez T, Sesen J, Nasim S, Lang SS, Heuer G, Tucker A, Lopez-Ramirez MA, Smith ER, Ghalali A. Lectin-type oxidized LDL receptor-1 as a potential therapeutic target for cerebral cavernous malformations treatment. Front Neurosci. 2024 Aug 21:18:1442110.