Peripheral Blood MCEMP1 Gene Expression as a Biomarker for Stroke Prognosis

Abstract

−4). MCEMP1 was also highest soon after symptom onset and had no association with stroke risk factors. Furthermore, MCEMP1 expression independently improved discrimination of 1-month outcome. Indeed, discrimination models for disability and mortality that included MCEMP1 expression, baseline modified Rankin Scale score, and primary stroke type improved discrimination when compared with a model without MCEMP1 (disability Net Reclassification Index, 0.76; P=3.0×10 −6 and mortality Net Reclassification Index, 1.3; P=1.1×10). Significant associations with MCEMP1 were confirmed in an independent validation cohort of 28 stroke cases and 34 controls. Conclusions-This study demonstrates that peripheral blood expression of MCEMP1 may have utility for stroke diagnosis and as a prognostic biomarker of stroke outcome at 1-month. (Stroke. 2016;47:652-658.

Shifts in Leukocyte Counts Drive the Differential Expression of Transcriptional Stroke Biomarkers in Whole Blood

“…Without additional experimentation, it is impossible to determine which genes are differentially expressed simply as artifacts of the stroke-induced shift in WBC differential, and which are differentially expressed due to true transcriptional modifications at the cellular level; the inability to make this distinction makes the identification of pathologically relevant genes difficult. However, a majority of genomewide stroke transcriptomics investigations performed in whole blood have interpreted their results under the assumption that all observed differential expression is a result of true cellular alterations in transcription [1][2][3][4][5]. Our findings clearly infer that this assumption is likely untrue, as it is highly likely that several genes identified as being differentially expressed in these previous studies undergo altered expression via a similar mechanism as the ten which we assessed in our analysis.…”

“…The identification of circulating biomarkers which could be used to accurately detect stroke would allow for the development of molecular diagnostics which could better inform triage and treatment decisions in the acute phase of care. The peripheral immune system responds robustly to stroke, and multiple genome-wide transcriptomic studies have demonstrated that stroke induces widespread alterations in gene expression at the level of whole blood [1][2][3][4][5]. Recently, our group leveraged this phenomenon to identify a blood-based RNA panel consisting of seven upregulated genes (PLXDC2, STK3, ANTXR2, KIF1B, CD163, PDK4, CTSZ) and three downregulated genes (GRAP, MAL, ID3) which has demonstrated the ability to accurately detect acute ischemic stroke (AIS) in three independent patient populations [3,6].…”

Whole Blood Gene Expression Differentiates between Atrial Fibrillation and Sinus Rhythm after Cardioversion

“…As such the impact of shorter fasting episodes on gene expression, as in our study, has yet to be published. We have evaluated expression of SLC25A20 and PDK4 in a control population [ 30 ] for up to 12 hours of fasting and observed no association between expression and hours since last meal (p>0.5 = NS , S6 Fig ). The significance of SLC25A20 and PDK4 in AF is further supported by the atrial tissue study that observed elevated expression of both genes in AF patients as compared with patients in sinus rhythm that had a history of AF [ 11 ].…”

Development of a Bioinformatics Framework for Identification and Validation of Genomic Biomarkers and Key Immunopathology Processes and Controllers in Infectious and Non-infectious Severe Inflammatory Response Syndrome

“…Its role in cellular processes in this context are not known, however, it may be associated with protection from or response to oxidative stress (165), as hypoxia is a common feature of sepsis (166)(167)(168)(169) and may have an effect on immune cell function (170). C19orf59 (or MCEMP1) was originally identified as a Mast cell-associated protein (171) and is a peripheral blood biomarker for patients with stroke (172)(173)(174). However, it also constitutes a component of neutrophil exosomes and myeloid suppressor cell exosomes (175).…”