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Circulating MicroRNAs as potential risk biomarkers for hematoma enlargement after intracerebral hemorrhage.

ABSTRACT: BACKGROUND AND PURPOSE:MicroRNAs have recently been shown to regulate the downstream bioprocesses of intracerebral hemorrhage. The aim of this study was to investigate whether miRNAs can be used as biomarkers to predict secondary hematoma enlargement (HE) in patients with ICH. METHODS:Consecutively, 79 ICH patients admitted within 6 h of symptom onset and 30 healthy individuals were enrolled in this study. Whole-genome miRNA expression profiles were generated in 32 patients (HE/non-HE: 14/18). Representative differentially expressed miRNAs were measured in all cases (HE/non-HE: 30/49) and normal controls (n = 30) by real-time PCR. RESULTS:Thirty miRNAs showed differential expressions in the plasma samples from patients with HE as compared with the non-HE controls. Compared to the hierarchical cluster analysis with all probes on microarray, all patients were separated into two main branches with only four exceptions by 30 differentially expressed miRNAs, improving the overall accuracy from 47.62 to 77.78% in the HE and 72.73 to 100% in the non-HE group. Further support vector machine (SVM) test can discriminate the two groups with 100% accuracy with 10 differentially expressed miRNAs. CONCLUSIONS:We demonstrated that multiple miRNAs are differentially expressed in the plasma of ICH patients with or without HE and may serve as circulating biomarkers for predicting HE after ICH.

SUBMITTER: Zheng HW

PROVIDER: S-EPMC6493543 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Circulating MicroRNAs as potential risk biomarkers for hematoma enlargement after intracerebral hemorrhage.

Zheng Hong-Wei HW Wang Yi-Long YL Lin Jin-Xi JX Li Na N Zhao Xing-Quan XQ Liu Gai-Fen GF Liu Li-Ping LP Jiao Yan Y Gu Wei-Kuan WK Wang David Z DZ Wang Yong-Jun YJ

CNS neuroscience & therapeutics 20121201 12

<h4>Background and purpose</h4>MicroRNAs have recently been shown to regulate the downstream bioprocesses of intracerebral hemorrhage. The aim of this study was to investigate whether miRNAs can be used as biomarkers to predict secondary hematoma enlargement (HE) in patients with ICH.<h4>Methods</h4>Consecutively, 79 ICH patients admitted within 6 h of symptom onset and 30 healthy individuals were enrolled in this study. Whole-genome miRNA expression profiles were generated in 32 patients (HE/no ...[more]

PMID: 23190933

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Project description:ObjectiveHematoma enlargement (HE) is associated with clinical outcomes after supratentorial intracerebral hemorrhage (ICH). This study evaluates whether HE characteristics and association with functional outcome differ in deep versus lobar ICH.MethodsPooled analysis of individual patient data between January 2006 and December 2015 from a German-wide cohort study (RETRACE, I + II) investigating ICH related to oral anticoagulants (OAC) at 22 participating centers, and from one single-center registry (UKER-ICH) investigating non-OAC-ICH patients. Altogether, 1954 supratentorial ICH patients were eligible for outcome analyses, which were separately conducted or controlled for OAC, that is, vitamin-K-antagonists (VKA, n = 1186) and non-vitamin-K-antagonist-oral-anticoagulants (NOAC, n = 107). Confounding was addressed using propensity score matching, cox regression modeling and multivariate modeling. Main outcomes were occurrence, extent, and timing of HE (>33%/>6 mL) and its association with 3-month functional outcome.ResultsOccurrence of HE was not different after deep versus lobar ICH in patients with non-OAC-ICH (39/356 [11.0%] vs. 36/305 [11.8%], P = 0.73), VKA-ICH (249/681 [36.6%] vs. 183/505 [36.2%], P = 0.91), and NOAC-ICH (21/69 [30.4%] vs. 12/38 [31.6%], P = 0.90). HE extent did not differ after non-OAC-ICH (deep:+59% [40-122] vs. lobar:+74% [37-124], P = 0.65), but both patients with VKA-ICH and NOAC-ICH showed greater HE extent after deep ICH [VKA-ICH, deep: +94% [54-199] vs. lobar: +56% [35-116], P < 0.001; NOAC-ICH, deep: +74% [56-123] vs. lobar: +40% [21-49], P = 0.001). Deep compared to lobar ICH patients had higher HE hazard during first 13.5 h after onset (Hazard ratio [HR]: 1.85 [1.03-3.31], P = 0.04), followed by lower hazard (13.5-26.5 h, HR: 0.46 [0.23-0.89], P = 0.02), and equal hazard thereafter (HR: 0.96 [0.56-1.65], P = 0.89). Odds ratio for unfavorable outcome was higher after HE in deep (4.31 [2.71-6.86], P < 0.001) versus lobar ICH (2.82 [1.71-4.66], P < 0.001), and only significant after small-medium (1st volume-quarter, deep: 3.09 [1.52-6.29], P < 0.01; lobar: 3.86 [1.35-11.04], P = 0.01) as opposed to large-sized ICH (4th volume-quarter, deep: 1.09 [0.13-9.20], P = 0.94; lobar: 2.24 [0.72-7.04], P = 0.17).InterpretationHE occurrence does not differ among deep and lobar ICH. However, compared to lobar ICH, HE after deep ICH is of greater extent in OAC-ICH, occurs earlier and may be of greater clinical relevance. Overall, clinical significance is more apparent after small-medium compared to large-sized bleedings.

Project description:BackgroundEarly hematoma growth is associated with poor functional outcomes in patients with intracerebral hemorrhage (ICH). We aimed to explore whether quantitative hematoma heterogeneity in non-contrast computed tomography (NCCT) can predict early hematoma growth.MethodsWe used data from the Risk Stratification and Minimally Invasive Surgery in Acute Intracerebral Hemorrhage (Risa-MIS-ICH) trial. Our study included patients with ICH with a time to baseline NCCT <12 h and a follow-up CT duration <72 h. To get a Hounsfield unit histogram and the coefficient of variation (CV) of Hounsfield units (HUs), the hematoma was segmented by software using the auto-segmentation function. Quantitative hematoma heterogeneity is represented by the CV of hematoma HUs. Multivariate logistic regression was utilized to determine hematoma growth parameters. The discriminant score predictive value was assessed using the area under the ROC curve (AUC). The best cutoff was determined using ROC curves. Hematoma growth was defined as a follow-up CT hematoma volume increase of >6 mL or a hematoma volume increase of 33% compared with the baseline NCCT.ResultsA total of 158 patients were enrolled in the study, of which 31 (19.6%) had hematoma growth. The multivariate logistic regression analysis revealed that time to initial baseline CT (P = 0.040, odds ratio [OR]: 0.824, 95 % confidence interval [CI]: 0.686-0.991), "heterogeneous" in the density category (P = 0.027, odds ratio [OR]: 5.950, 95 % confidence interval [CI]: 1.228-28.828), and CV of hematoma HUs (P = 0.018, OR: 1.301, 95 % CI: 1.047-1.617) were independent predictors of hematoma growth. By evaluating the receiver operating characteristic curve, the CV of hematoma HUs (AUC = 0.750) has a superior predictive value for hematoma growth than for heterogeneous density (AUC = 0.638). The CV of hematoma HUs had an 18% cutoff, with a specificity of 81.9 % and a sensitivity of 58.1 %.ConclusionThe CV of hematoma HUs can serve as a quantitative hematoma heterogeneity index that predicts hematoma growth in patients with early ICH independently.

Dataset Information

Circulating MicroRNAs as potential risk biomarkers for hematoma enlargement after intracerebral hemorrhage.

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Circulating MicroRNAs as potential risk biomarkers for hematoma enlargement after intracerebral hemorrhage.

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