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Published on: September 25, 2016
Combined Omic Analyzes of Cerebral Thrombi: A New Molecular Approach to Identify Cardioembolic Stroke Origin
Laurent Suissa1,2,3, Jean-Marie Guigonis1, Fanny Graslin1
1Laboratory Transporter in Imaging and Radiotherapy in Oncology (TIRO), Direction de la Recherche Fondamentale (DRF), Institut des sciences du vivant Fréderic Joliot, Commissariat à l'Energie Atomique et aux énergies alternatives (CEA), Université Côte d'Azur (UCA), Nice, France (L.S., J.-M.G., F.G., S.L., T.P.).
Insights
Analyzing cerebral thrombi using proteomic and metabolomic methods can accurately identify cardioembolic stroke origins. This molecular approach significantly improves stroke diagnosis and secondary prevention strategies.
Area of Science:
- Neuroscience
- Biochemistry
- Genomics
Background:
- Diagnosing cardioembolic stroke is challenging for secondary stroke prevention, especially with covert paroxysmal atrial fibrillation.
- Cerebral thrombus molecular composition varies by origin, suggesting potential for etiological diagnosis via analysis.
- Proteomic and metabolomic analyses of retrieved thrombi may identify biomarkers for improved stroke etiological diagnosis.
Purpose of the Study:
- To investigate the proteomic and metabolomic profiles of cerebral thrombi in atherothrombotic and cardioembolic stroke patients.
- To identify molecular signatures for improved etiological diagnosis of stroke.
- To compare the diagnostic performance of omic signatures with classical stroke predictors.
Main Methods:
- Pilot study analyzing proteome and metabolome of cerebral thrombi from stroke patients using ASCOD phenotyping.
- Utilized untargeted proteomic and metabolomic approaches on thrombi from the ThrombiOMIC cohort.
- Compared omic signatures (proteomic, metabolomic, combined) with classical predictors (e.g., BNP) using ROC analysis.
Main Results:
- Identified 2,456 proteins and 5,019 molecular features in cerebral thrombi.
- Combined proteomic and metabolomic signatures achieved high diagnostic performance (AUC 0.996) for cardioembolic stroke.
- Combined omic signatures significantly outperformed plasmatic BNP levels (AUC 0.803) in predicting cardioembolic origin.
Conclusions:
- Combined proteomic and metabolomic analysis of cerebral thrombi is a promising approach for predicting stroke etiology.
- This molecular strategy can enhance secondary stroke prevention strategies.
- The findings support the use of thrombus analysis for improved etiological diagnosis in stroke patients.
Background And Purpose:
The diagnosis of cardioembolic stroke can be challenging for patient management in secondary stroke prevention, particularly in the case of covert paroxysmal atrial fibrillation. The molecular composition of a cerebral thrombus is related to its origin. Therefore, proteomic and metabolomic analyses of the retrieved thrombotic material should allow the identification of biomarkers or signatures to improve the etiological diagnosis of stroke.
Methods:
In this pilot study, the proteome and metabolome of cerebral thrombi from atherothrombotic and cardioembolic stroke patients were studied according to ASCOD phenotyping (A: atherosclerosis; S: small-vessel disease; C: cardiac pathology; O: other causes; D: dissection), with the highest causality grade, from the ThrombiOMIC cohort (consecutive patients with stroke recanalized by mechanical thrombectomy in an acute phase). Proteomic and metabolomic results were used separately or combined, and the obtained omic signatures were compared with classical cardioembolic stroke predictors using pairwise comparisons of the area under receiver operating characteristics.
Results:
Among 59 patients of the ThrombiOMIC cohort, 34 patients with stroke showed a cardioembolic phenotype and 7 had an atherothrombotic phenotype. Two thousand four hundred fifty-six proteins and 5019 molecular features of the cerebral thrombi were identified using untargeted proteomic and metabolomic approaches, respectively. Area under receiver operating characteristics to predict the cardioembolic origin of stroke were calculated using the proteomic results (0.945 [95% CI, 0.871–1]), the metabolomic results (0.836 [95% CI, 0.714–0.958]), and combined signatures (0.996 [95% CI, 0.984–1]). The diagnostic performance of the combined signatures was significantly higher than that of classical predictors such as the plasmatic BNP (B-type natriuretic peptide) level (area under receiver operating characteristics, 0.803 [95% CI, 0.629–0.976]).
Conclusions:
The combined proteomic and metabolomic analyses of retrieved cerebral thrombi is a very promising molecular approach to predict the cardioembolic cause of stroke and to improve secondary stroke prevention strategies.
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