Identification of novel biomarkers for prediction of neurological prognosis following cardiac arrest.
BACKGROUND
Early prognostication of neurological outcome in comatose patients after cardiac arrest (CA) is important for devising patient treatment strategies. However, there is still a lack of sensitive and specific biomarkers for easy identification of these patients. We evaluated whether molecular signatures from blood of CA patients might help to improve the prediction of neurological outcome.


METHODS
We examined 22 comatose patients resuscitated after CA and obtained peripheral blood samples 48 hours after CA. To identify novel blood biomarkers, we aimed to measure neurological outcomes according to the Cerebral Performance Category (CPC) score at 6 months after CA and to determine blood transcriptome-based molecular signature of poor neurological outcome group.


RESULTS
According to the CPC score, 10 patients exhibited a CPC score of one and 12 patients, a CPC score four to five. Blood transcriptomics revealed differently expressed profiles between the good outcome group and poor outcome group. A total of 150 genes were down-regulated and 237 genes were up-regulated in the poor neurological outcome group compared with good outcome group. From the blood transcriptome-based signatures, we identified that MAPK3, BCL2 and AKT1 were more specific and sensitive diagnostic biomarkers in poor neurological outcome with an area under the curve of 0.867 (p<0.0001), 0.800 (p=0.003), and 0.767 (p=0.016) respectively.


CONCLUSIONS
We identify three biomarkers as potential predictors of neurological outcome following CA. Further assessment of the prognostic value of transcriptomic analysis in larger cohorts of CA patients is needed.
Department of Pathology, Functional RNomics Research Center, Cancer Evolution Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Jung Woo
JW
Eun
Department of Pathology, Functional RNomics Research Center, Cancer Evolution Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Hee Doo
HD
Yang
Department of Emergency Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Soo Hyun
SH
Kim
Department of Emergency Medicine, College of Medicine, The Catholic University of Korea, Daejeon, Republic of Korea.
Sungyoup
S
Hong
Department of Emergency Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Kyu Nam
KN
Park
Department of Pathology, Functional RNomics Research Center, Cancer Evolution Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Suk Woo
SW
Nam
Department of Emergency Medicine, College of Medicine, The Catholic University of Korea, Daejeon, Republic of Korea.
Sikyoung
S
Jeong
D015415:Biomarkers / Q000097:blood; D016000:Cluster Analysis; D003128:Coma / Q000097:blood / Q000209:etiology / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006323:Heart Arrest / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D048052:Mitogen-Activated Protein Kinase 3 / Q000097:blood / Q000235:genetics*; D017063:Outcome Assessment, Health Care; D011237:Predictive Value of Tests; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000097:blood / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000097:blood / Q000235:genetics*; D012151:Resuscitation; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015415:Biomarkers; D019253:Proto-Oncogene Proteins c-bcl-2; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D048052:Mitogen-Activated Protein Kinase 3
Pathology Section; cardiac arrest; cerebral performance category; molecular signature; neurological prognosis; peripheral blood transcriptome