Long noncoding RNA LINC00152 is a potential prognostic biomarker in patients with high-grade glioma.

AIMS: To investigate the role of LINC00152 in high-grade glioma (HGG). METHODS: We collected data from the Chinese Glioma Genome Atlas (CGGA) microarray, CGGA RNA sequencing, and GSE16011 datasets to evaluate the expression and prognostic relationship of LINC00152 in patients with HGGs. A knockdown assay was performed to determine the function of LINC00152 in glioma development and progression in vitro and in vivo. RESULTS: The expression of LINC00152 was increased with glioma grade, especially in the mesenchymal TCGA subtype. LINC00152 was independently associated with poor prognosis, and the overall survival (OS) of the high expression group was shorter than the low expression group (median OS 14.77 vs 9.65 months; P = 0.0216) in the CGGA microarray dataset. The results were validated in the other 2 datasets. Based on the expression of LINC00152, 4288 (2519 positively; 1769 negatively) probes were extracted to perform a biological process analysis using the Database for Annotation, Visualization, and Integrated Discovery. Positively regulated genes were enriched in immune response, apoptotic process, cell adhesion, and regulation of cell proliferation. The clinical and molecular features of HGG patients indicated that patients in the LINC00152 high expression group tended to display the mesenchymal type, older (≥46 years), isocitrate dehydrogenase1 wild-type, O(6)-methylguanine DNA methyltransferase unmethylated, nonchemotherapy, and low karnofsky performance status. Functionally, knockdown of LINC00152 inhibited cell proliferation, migration, and invasion and increased the sensitivity of chemotherapy in vitro. CONCLUSION: Our results indicate that knockdown of LINC00152 could inhibit tumor growth in vivo. LINC00152 could serve as a potential prognostic biomarker in patients with HGG.

Prognostic value of MGMT promoter methylation and TP53 mutation in glioblastomas depends on IDH1 mutation.

Several molecular markers have been proposed as predictors of outcome in patients with glioblastomas. We investigated the prognostic significance of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and TP53 mutation status dependent on isocitrate dehydrogenase 1 (IDH1) mutation in glioblastoma patients. A cohort of 78 patients with histologically confirmed glioblastomas treated with radiation therapy and chemotherapy were reviewed retrospectively. We evaluated the prognostic value of MGMT promoter methylation and TP53 mutation status with regard to progression-free survival (PFS) and overall survival (OS). It was revealed that mutations in IDH1, promoter methylation of MGMT, TP53 mutation, age, Karnofsky performance status (KFS), and extension of resection were independent prognostic factors. In patients with an IDH1 mutation, those with an MGMT methylation were associated with longer PFS (p=0.016) and OS (p=0.013). Nevertheless, the presence of TP53 mutation could stratify the PFS and OS of patients with IDH1 wild type (p=0.003 and 0.029 respectively, log-rank). The MGMT promoter methylation and TP53 mutation were associated with a favorable outcome of patients with and without mutant IDH1, respectively. The results indicate that glioblastomas with MGMT methylation or TP53 mutations have improved survival that may be influenced by IDH1 mutation status.

Plasma levels of tissue inhibitor of matrix metalloproteinase-1 correlate with diagnosis and prognosis of glioma patients.

BACKGROUND: There is no validated blood biomarker available for glioma management. Invasive growth is the key feature of glioma. We assessed the clinical usefulness of plasma tissue inhibitor of metalloproteinase 1 (TIMP-1), which has less molecular weight than metalloproteinases, as a potential blood biomarker for glioma. METHODS: A total of 285 patients and 59 normal subjects were studied. Plasma concentration of TIMP-1 was measured with enzyme-linked immunosorbent assay. Plasma TIMP-1 was compared between normal and glioma patients, between patients with different pathological grades, and between patients with different prognoses. Longitudinal changes in plasma TIMP-1 during treatment were also evaluated. Plasma matrix metalloproteinase (MMP)-9 level was also assayed and its clinical usefulness was compared with that of TIMP-1. RESULTS: Plasma TIMP-1 and MMP-9 were both increased in glioma patients compared with normal controls (TIMP-1: P < 0.001; MMP-9: P = 0.007). Plasma TIMP-1 increases with increased tumor grade. In Grade IV gliomas, plasma TIMP-1 significantly increased after "successful removal" of the tumor (paired samples t-test, before operation vs. during chemotherapy without recurrence, t = -2.131, P = 0.038), but did not change significantly at the time of tumor recurrence (during chemotherapy without recurrence vs. after tumor recurrence, t = -0.652, P = 0.632). High plasma TIMP-1 level correlated with better survival in Grade IV glioma patients (hazard ratio: 0.550, 95% CI: 0.101-1.000, P = 0.036). In Grade IV gliomas, patients with higher plasma TIMP-1 had significantly longer survival time than those with lower plasma TIMP-1 level (25.23 vs. 18.95 months, log-rank P = 0.045). Plasma MMP-9 did not show significant association with either the pathological grade or the prognosis of glioma patients. CONCLUSIONS: Plasma TIMP-1 is associated with the diagnosis and prognosis of glioma patients. It appears to have better usefulness for guiding clinical decision making than plasma MMP-9. Further studies in an expanded patient population are needed to better define its clinical usefulness.

Increase of plasma IgE during treatment correlates with better outcome of patients with glioblastoma.

BACKGROUND: Previous studies have shown that glioma patients have lower blood IgE levels than controls. To evaluate its potential as a surrogate biomarker for glioma, we measured plasma IgE levels in glioma patients and healthy controls, and correlated them with clinicopathological factors and the patients' outcome. METHODS: We used enzyme-linked immunosorbant assay (ELISA) to determine the plasma IgE levels of 25 normal subjects and 252 glioma patients (85 patients with grade II glioma, 46 patients with grade III glioma, and 121 patients with glioblastoma). We also collected longitudinal plasma samples from glioblastoma patients and compared the plasma IgE levels before operation, one week after operation, in the middle of radiotherapy, after two cycles of chemotherapy, and after recurrence. The correlations between plasma IgE levels and the outcomes of the patients were determined. RESULTS: Plasma IgE levels were significantly lower in glioma patients (P = 0.004); patients with low-grade glioma have lower IgE levels than patients with high-grade glioma do (P = 0.029). In 24 patients with both preoperative plasma and two-cycle chemotherapy plasma samples, IgE levels increased after successful removal of the tumor (P = 0.021), and the increase correlated with the patients' survival (increase > 100 ng/ml vs. ≤ 100 ng/ml, 127.5 weeks vs. 62.3 weeks. P = 0.012, log-rank). Plasma IgE level increase of > 100 ng/ml has a specificity of 80% and a sensitivity of 78% to predict the patients' long survival (> 18 months). CONCLUSIONS: Our results suggest that plasma IgE level correlates with clinical and pathological factors in glioma patients. It has the potential to be a biomarker for glioma patients.

Preoperative 3T high field blood oxygen level dependent functional magnetic resonance imaging for glioma involving sensory cortical areas.

BACKGROUND: Localization of sensory cortical areas during the operation is essential to preserve the sensory function. Intraoperative direct electrostimulation under awake anesthesia is the golden standard but time-consuming. We applied 3T high field blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to identify the relationship between glioma and cortical sensory areas preoperatively and to guide intraoperative direct electrostimulation for quick and precise localization. METHODS: Five glioma patients with sensory cortex involvement by or next to the lesion had preoperative BOLD fMRI to determine the spatial relationship of cortical sensory areas to the tumours. Bilateral hand opposite movement was performed by these patients for fMRI. Precentral and postcentral gyri were identified by electrical stimulation during the operation. Karnofsky Performance Status scores of the patients' pre- and postoperative and the role of BOLD fMRI were evaluated. RESULTS: The cortical sensory areas were all activated in five glioma patients involving postcentral gyrus areas by BOLD fMRI with bilateral hand opposite movement. The detected activation areas corresponded with the results from cortical electrical stimulation. CONCLUSIONS: The relationship between cortical sensory areas and tumour can be accurately shown by BOLD fMRI before operation. And the information used to make the tumour resection could obtain good clinical results.

Blood-brain barrier penetration of cefepime after neurosurgery.

BACKGROUND: It has been confirmed that the concentration of cefepime in cerebrospinal fluid (CSF) could reach the 10% of its concentration in plasma, exceeding the inhibitory concentration to 90% of organisms (MIC(90)) for common bacteria. However, the blood-brain barrier (BBB) penetration ability of cefepime is still unclear. The aim of this study was to measure the CSF concentration of cefepime in patients after neurosurgical operations, and to determine the penetration of the drug through an incomplete BBB. METHODS: Eight patients who received ventricular drainage (VD group) and 5 who underwent lumbar puncture drainage (LPD group) were enrolled into this study. Cefepime (2 g) was injected intravenously in 30 minutes after the neurosurgeries. The concentrations of cefepime in the CSF and plasma were measured by high-pressure liquid chromatography (HPLC) at different time points. RESULTS: The CSF concentrations of cefepime at different time points in the VD group were significantly higher than those in the LPD group (P < 0.05). In the VD group, the concentration of cefepime in CSF reached the peak ((22.54 +/- 14.06) microg/ml) at 1 to 2 hours after the injection, while in the LPD group at 4 hours ((5.61 +/- 3.73) microg/ml). In both groups, the peak was higher than the MIC(90) of most common bacteria in intensive care unit. The ratio of CSF to plasma cefepime concentrations ranged from 0.30 to 2.14 in the VD group and 0.03 to 1.14 in the LPD group. CONCLUSION: After neurosurgeries, CSF concentration of cefepime can reach a therapeutic level. Thus, the drug could be used to prevent and treat postoperative intracranial infection.

A study on the relationship between HLA-DR, DQ antigen, and intracranial aneurysm in the Han nationality.

BACKGROUND: To investigate the relationship between HLA-DR, DQ antigen, and intracranial aneurysm in the Han nationality. METHODS: We compared the occurrence of HLA-DR and HLA-DQ antigens in patients with intracranial saccular aneurysm and in the control group by PCR and agarose gel electrophoresis. RESULTS: No statistically significant correlation between HLA-DR, HLA-DQ antigen frequency, and the pathogenesis and clinical characteristics of intracranial aneurysm has been found. CONCLUSIONS: We have not found any relationship between HLA-DR and HLA-DQ antigen frequency, haplotype frequency, and pathogenesis and clinical characteristics of intracranial aneurysm, but the patients who presented with HLA-DR53, DR52, DQ7(3), and DQ5(1) seem to be more likely to bear multiple intracranial aneurysms.