Protein Biomarkers in Blood Reflect the Interrelationships Between Stroke Outcome, Inflammation, Coagulation, Adhesion, Senescence and Cancer

The most important predictors for outcomes after ischemic stroke, that is, for health deterioration and death, are chronological age and stroke severity; gender, genetics and lifestyle/environmental factors also play a role. Of all these, only the latter can be influenced after the event. Recurrent stroke may be prevented by antiaggregant/anticoagulant therapy, angioplasty of high-grade stenoses, and treatment of cardiovascular risk factors. Blood cell composition and protein biomarkers such as C-reactive protein or interleukins in serum are frequently considered as biomarkers of outcome. Here we aim to provide an up-to-date protein biomarker signature that allows a maximum of mechanistic understanding, to predict health deterioration following stroke. We thus surveyed protein biomarkers that were reported to be predictive for outcome after ischemic stroke, specifically considering biomarkers that predict long-term outcome (>= 3 months) and that are measured over the first days following the event. We classified the protein biomarkers as immune-inflammatory, coagulation-related, and adhesion-related biomarkers. Some of these biomarkers are closely related to cellular senescence and, in particular, to the inflammatory processes that can be triggered by senescent cells. Moreover, the processes that underlie inflammation, hypercoagulation and cellular senescence connect stroke to cancer, and biomarkers of cancer-associated thromboembolism, as well as of sarcopenia, overlap strongly with the biomarkers discussed here. Finally, we demonstrate that most of the outcome-predicting protein biomarkers form a close-meshed functional interaction network, suggesting that the outcome after stroke is partially determined by an interplay of molecular processes relating to inflammation, coagulation, cell adhesion and cellular senescence.

Automated summary

The most important predictors for outcomes after ischemic stroke are chronological age and stroke severity, with gender, genetics, and lifestyle/environmental factors also playing a role. Recurrent stroke can be prevented through various therapies and treatment of risk factors. Protein biomarkers, particularly those related to immune-inflammatory, coagulation, and adhesion processes, can provide insight into predicting health deterioration following stroke. These processes also connect stroke to cancer and other conditions, indicating potential overlap in biomarkers.