Plasma biglycan identified by DIA proteomics as a biomarker for differential diagnosis of perimesencephalic non-aneurysmal and aneurysmal subarachnoid hemorrhage.

Objective

The aim of this study is to elucidate the molecular heterogeneity of perimesencephalic non-aneurysmal subarachnoid hemorrhage (pmSAH), non-perimesencephalic non-aneurysmal subarachnoid hemorrhage (npmSAH) and aneurysmal subarachnoid hemorrhage (aSAH), reveal the unique pathological features of pmSAH, and screen the specific plasma biomarkers that can be used to identify pmSAH.

Methods

Data independent acquisition mass spectrometry was used to analyze the plasma proteome. The differentially abundence proteins were analyzed by PPI network construction, GO and KEGG pathway enrichment analysis to explore the unique functional characteristics and potential biological mechanisms of different SAH. The characteristic proteins of pmSAH and aSAH were screened to construct a differential system that can positively define pmSAH and inversely exclude aSAH to improve the diagnostic specificity. The receiver operating characteristic curve was used to evaluate the diagnostic value of the candidate biomarkers.

Results

20 candidate biomarkers specific for pmSAH and 42 candidate biomarkers specific for aSAH were obtained. ASAH and npmSAH were mainly enriched in pathways related to aneurysm formation, vessel wall injury and inflammatory activation. PmSAH was particularly enriched in pathways related to vascular repair and homeostasis regulation. In particular, the plasma biglycan (BGN) concentration was significantly increased in pmSAH and decreased in aSAH. After validation, BGN may serve as a biomarker for differentiating pmSAH from aSAH. The area under the receiver operator characteristic curve was 0.754, the specificity was 71.9 %, and the sensitivity was 71.9 %.

Conclusion

Our study revealed that BGN is a potential biomarker for distinguishing pmSAH from aSAH.