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Interleukin-6 as a Prognostic Biomarker in Ruptured Intracranial Aneurysms.

ABSTRACT: Interleukin-6 (IL-6), a proinflammatory cytokine, was found to surge in the cerebral spinal fluid after aneurysmal subarachnoid hemorrhage (SAH). We hypothesized that the plasma level of IL-6 could be an independent biomarker in predicting clinical outcome of patients with ruptured intracranial aneurysm.We prospectively included 53 consecutive patients treated with platinum coil embolization of the ruptured intracranial aneurysm. Plasma IL-6 levels were measured in the blood samples at the orifices of the aneurysms and from peripheral veins. The outcome measure was the modified Rankin Scale one month after SAH. Multiple logistic regression analyses were used to evaluate the associations between the plasma IL-6 levels and the neurological outcome.Significant risk factors for the poor outcome were old age, low Glasgow Coma Scale (GCS) on day 0, high Fisher grades, and high aneurysmal and venous IL-6 levels in univariate analyses. Aneurysmal IL-6 levels showed modest to moderate correlations with GCS on day 0, vasospasm grade and Fisher grade. A strong correlation was found between the aneurysmal and the corresponding venous IL-6 levels (ρ = 0.721; P<0.001). In the multiple logistic regression models, the poor 30-day mRS was significantly associated with high aneurysmal IL-6 level (OR, 17.97; 95% CI, 1.51-214.33; P = 0.022) and marginally associated with high venous IL-6 level (OR, 12.71; 95% CI, 0.90-180.35; P = 0.022) after adjusting for dichotomized age, GCS on day 0, and vasospasm and Fisher grades.The plasma level of IL-6 is an independent prognostic biomarker that could be used to aid in the identification of patients at high-risk of poor neurological outcome after rupture of the intracranial aneurysm.

SUBMITTER: Kao HW

PROVIDER: S-EPMC4503596 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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Project description:Background: Ruptured intracranial aneurysm (IA) is a disease with high mortality. Despite the great progress in treating ruptured IA, methods for risk assessment of ruptured IA remain limited. Methods: In this study, we aim to develop a robust diagnostic model for ruptured IA. Gene expression profiles in blood samples of 18 healthy persons and 43 ruptured IA patients were obtained from the Gene Expression Omnibus (GEO). Differential expression analysis was performed using limma Bioconductor package followed by functional enrichment analysis via clusterProfiler Bioconductor package. Immune cell compositions in ruptured IA and healthy samples were assessed through the CIBERSORT tool. Protein-protein interaction (PPI) was predicted based on the STRING database. Logistic regression model was used for the construction of predictive model for distinguishing ruptured IA and healthy samples. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to validate the gene expression between the ruptured IA and healthy samples. Results: A total of 58 differentially expressed genes (DEGs) were obtained for ruptured IA patients compared with healthy controls. Functional enrichment analysis showed that the DEGs were enriched in biological processes related to neutrophil activation, neutrophil degranulation, and cytokine-cytokine receptor interaction. Notably, immune analysis results proved that the rupture of IA might be related to immune cell distribution. We further identified 24 key genes as hub genes using the PPI networks. The logistic regression model trained based on the 24 key genes ultimately retained two genes, i.e., IL2RB and CCR7, which had great potential for risk assessment for rupture of IA. The RT-qPCR further validated that compared with the healthy samples, the expression levels of IL2RB and CCR7 were decreased in ruptured IA samples. Conclusions: This study might be helpful for cohorts who have a high risk of ruptured IA for early diagnosis and prevention of the disease.

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Interleukin-6 as a Prognostic Biomarker in Ruptured Intracranial Aneurysms.

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