title: Gene expression profiling of blood in ruptured intracranial aneurysms: in search of biomarkers.
abstract: The molecular mechanisms underlying the systemic response to subarachnoid hemorrhage (SAH) from ruptured intracranial aneurysms (RAs) are not fully understood. We investigated whether the analysis of gene expression in peripheral blood could provide clinically relevant information regarding the biologic consequences of SAH. Transcriptomics were performed using Illumina HumanHT-12v4 microarrays for 43 RA patients and 18 controls (C). Differentially expressed transcripts were analyzed for overrepresented functional groups and blood cell type-specific gene expression. The set of differentially expressed transcripts was validated using quantitative polymerase chain reaction in an independent group of subjects (15 RA patients and 14 C). There were 135 differentially expressed genes (false discovery rate 1%, absolute fold change 1.7): the abundant levels of 78 mRNAs increased and 57 mRNAs decreased. Among RA patients, transcripts specific to T lymphocyte subpopulations were downregulated, whereas those related to monocytes and neutrophils were upregulated. Expression profiles of a set of 16 genes and lymphocyte-to-monocyte-and-neutrophil gene expression ratios distinguished RA patients from C. These results indicate that SAH from RAs strongly influences the transcription profiles of blood cells. A specific pattern of these changes suggests suppression in lymphocyte response and enhancements in monocyte and neutrophil activities. This is probably related to the immunodepression observed in SAH.
authors.affiliation: Department of Neurology, Jagiellonian University Medical College, Krakow, Poland. pera@su.krakow.pl
authors.forename: Joanna
authors.initials: J
authors.lastname: Pera
authors.forename: Michal
authors.initials: M
authors.lastname: Korostynski
authors.forename: Slawomir
authors.initials: S
authors.lastname: Golda
authors.forename: Marcin
authors.initials: M
authors.lastname: Piechota
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Dzbek
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Krzyszkowski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Dziedzic
authors.forename: Marek
authors.initials: M
authors.lastname: Moskala
authors.forename: Ryszard
authors.initials: R
authors.lastname: Przewlocki
authors.forename: Andrzej
authors.initials: A
authors.lastname: Szczudlik
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Slowik
mesh_terms: D017542:Aneurysm, Ruptured / Q000097:blood* / Q000150:complications; D001402:B-Lymphocytes / Q000201:enzymology / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006801:Humans; D002532:Intracranial Aneurysm / Q000097:blood* / Q000150:complications; D007694:Killer Cells, Natural / Q000201:enzymology / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism; D025341:Principal Component Analysis; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D012422:Rupture, Spontaneous; D013345:Subarachnoid Hemorrhage / Q000097:blood* / Q000209:etiology; D013601:T-Lymphocytes / Q000201:enzymology / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics*
chemical_list: D015415:Biomarkers