Plasma miR-126 and miR-143 as Potential Novel Biomarkers for Cerebral Atherosclerosis.

BACKGROUND: Cerebral atherosclerosis is the most important mechanism for ischemic stroke. However, specific plasma biomarkers to assess atherosclerosis susceptibility are still lacking. Circulating miRNAs have been shown to be promising biomarkers for various pathologic conditions. We investigated whether plasma miR-126 and miR-143 could be used as biomarkers for identifying and evaluating cerebral atherosclerosis. Results showed that miR-143 and miR-126 might participate in the process of atherosclerosis and were minimally affected by cerebral infarction. Using Pearson correlation analysis, we showed that miR-126 and miR-143 were correlated with the presence and severity of cerebral atherosclerosis. The ability of miR-126 and miR-143 to differentiate atherosclerosis patients from healthy controls was demonstrated via a receiving operating characteristic curve with high specificity and sensitivity. Our data thus indicate that miR-126 and miR-143 may be potential specific biomarkers for atherosclerosis.

SCAMP3 Promotes Glioma Proliferation and Indicates Unfavorable Prognosis via Multiple Pathways.

INTRODUCTION: The secretory carrier-associated membrane protein 3 (SCAMP3) is a component of post-Golgi membranes, functions as a protein carrier and is critical for subcellular protein transportation. Limited studies revealed an elevated expression of SCAMP3 in breast cancer and hepatocellular carcinoma; however, its role in glioma remains unknown. The aim of our study is to investigate the expression pattern and functional mechanisms of SCAMP3 in glioma. METHODS: mRNA and protein levels of SCAMP3 were examined in glioma tissues together with nontumorous brain tissues by using quantitative real-time-PCR and immunohistochemistry staining. The prognostic role of SCAMP3 in glioma was evaluated through univariate and multivariate analyses. In vitro and in vivo assays were conducted to explore the underlying mechanisms of SCAMP3-induced glioma progression. RESULTS: The expression level of SCAMP3 was higher in glioma tissues than that in normal brain tissues. High protein level of SCAMP3 was correlated with larger tumor size and advanced WHO grade. Glioma patients with high-SCAMP3 level had worse overall survival. In addition, SCAMP3 was defined as an independent risk factor of glioma prognosis. Cellular and xenograft studies revealed that SCAMP3 promotes glioma proliferation possibly through enhancing EGFR and mTORC1 signaling. DISCUSSION: Our studies revealed that high-SCAMP3 expression level was closely related to the unfavorable clinical features and poor prognosis of glioma patients. SCAMP3 may serve as an invaluable prognostic indicator and novel therapeutic target for glioma treatment.

Association of TRAIL and Its Receptors with Large-Artery Atherosclerotic Stroke.

OBJECTIVE: To investigate the association of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors, osteoprotegerin (OPG) and death receptor 5 (DR5) with large-artery atherosclerosis (LAA) stroke and its prognosis. METHODS: We included patients with LAA stroke (n = 132) according to the TOAST classification system and controls (n = 60). To evaluate the extent and severity of cerebral atherosclerosis, the LAA stroke group was subdivided into 3 subgroups by number of cerebral arteries with atherosclerotic stenosis (≥50%): single, double and multiple (≥3). Plasma levels of TRAIL, OPG and DR5 were measured by ELISA. Ordinal logistic regression was used to analyze the association between the plasma levels of TRAIL, OPG, DR5 and the severity of cerebral atherosclerosis. Prognosis was determined by the Modified Rankin Scale at 3 months after stroke. Receiver operating characteristic (ROC) curve was used to evaluated TRAIL as a predictor of prognosis. RESULTS: Plasma TRAIL level was significantly lower for LAA patients than controls (P<0.001), while plasma OPG and DR5 levels were higher (both P<0.001). Logistic regression analysis revealed that risk of severe cerebral atherosclerosis was reduced significantly with increased plasma level of TRAIL (OR 0.438; 95% CI 0.282-0.681; P<0.001), whereas increased with high plasma levels of OPG and DR5 (OR 2.707; 95% CI 1.702-4.302, P <0.001; OR 3.593; 95% CI 1.878-6.869, P <0.001). Plasma TRAIL level was negatively correlated with the prognosis (r = - 0.372, P <0.001). The optimal cut-off value of TRAIL for prognosis was 848.63 pg/mL. The sensitivity and specificity at this cut-off value were 63.1% and 86.2%, respectively. After adding the plasma TRAIL level into the multivariate model of ROC, the area under the ROC curve was increased from 0.639 to 0.785, but the change was not statistical significant (P = 0.146). CONCLUSIONS: TRAIL and its receptors OPG and DR5 may be involved in LAA stroke and the plasma level of TRAIL may be a biomarker predicting the severity of cerebral atherosclerosis and the prognosis of LAA stroke.