Expression of eIF4E Gene in Glioma and Its Sensitivity to Oxidative Stress.

Objective: Increased expression of eIF4E has been observed in various cancers, which makes eIF4E an attractive target of anticancer drugs. This study mainly discussed eIF4E gene expression in glioma and its sensitivity to oxidative stress (OS). Methods: Relevant data from The Cancer Genome Atlas (TCGA) database regarding eIF4E gene expression and its prognostic significance in glioma samples were analyzed. Additionally, we measured eIF4E at mRNA and protein levels in clinical samples collected between July 2019 and September 2021, as well as glioma cell strains. U251 cells cultured in vitro were treated with OS injury induced by hydrogen peroxide (H2O2) and then transfected with si-eIF4E to determine changes in cell multiplication, invasiveness, and migration capacities as well as apoptosis rate. ELISA quantified cell malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) concentrations, and flow cytometry measured reactive oxygen species (ROS) level. Results: In glioma samples from the TCGA database, eIF4E showed obviously elevated levels in LGG and GBM patients, which was usually associated with adverse patient prognosis (P < 0.05). eIF4E was also upregulated in glioma cell strains than in HBE cells. In comparison with the blank control group, transfection of si-eIF4E statistically suppressed the capacity of U251 cells to proliferate, invade and migrate, and enhance apoptosis rate, while reducing SOD and GSH-Px and increasing MDA and ROS. In addition, H2O2 induced the upregulation of eIF4E in U251 cells. H2O2 + si-eIF4E exhibited reduced multiplication and number of clone cell formation, invasion, and migration of U251 cells, as well as increased apoptosis rate than H2O2 + si-NC group. Conclusions: eIF4E is highly expressed in glioma. Knocking down eIF4E can effectively inhibit the capacity of U251 to proliferate, invade and migrate, and significantly increase apoptosis. In addition, eIF4E knock-down is able to lower OS reaction under H2O2 inducement and enhance U251 cells' sensitivity to OS.

Diagnostic and prognostic utility of eIF6 in glioblastoma: a study based on TCGA and CGGA databases.

BACKGROUND: Among various glioma types, glioblastoma multiforme (GBM) is one of those with the highest malignancy. Although overexpression of eukaryotic translation initiation factor 6 (eIF6), a factor that regulates protein translation initiation, is believed to promote tumor development, its function and potential molecular mechanisms in glioma progression remain uncharacterized. Consequently, we evaluated its diagnostic and prognostic utility in GBM patients. METHODS: Sample data from two databases, The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), were utilized to investigate the role of eIF6 as well as its mechanism of action in gliomas. We analyzed eIF6 expression in normal tissues as well as cancerous samples of different stages of glioma. The diagnostic and prognostic value of eIF6 were analyzed using the Receiver Operating Characteristic Curve (ROC) and Kaplan-Meier analysis, respectively. Furthermore, its underlying molecular mechanism in GBM was further revealed by gene set enrichment analysis (GSEA). RESULTS: Transcriptome data analyses of the two databases showed that eIF6 was upregulated in glioma tissues compared with normal counterparts. eIF6 was at high levels in WHO grade IV gliomas versus grade II and III gliomas (P<0.05). In addition, eIF6 was highly expressed in elderly and Asian glioma patients. Furthermore, eIF6 expression was found to be lower in isocitrate dehydrogenase (IDH)-mutated tumors. Patients with high eIF6 level presented shorter overall survival than cases with low eIF6 level (P<0.05), and eIF6 had favorable accuracy in predicting the prognosis of glioma patients. GSEA revealed that high eIF6 expression was mainly concentrated in cell cycle and DNA repair related pathways. CONCLUSIONS: eIF6 is highly expressed in gliomas and positively associated with the degree of malignancy. Patients with high eIF6 expression present poor survival. Therefore, eIF6 has the potential to be a diagnostic biomarker and a potential therapeutic target for glioma development and GBM.

Relapsing MOG-IgG-associated diseases coexisting with anti-NMDAR encephalitis: a case report and literature review.

BACKGROUND: In recent years, an overlapping syndrome, MNOS, of MOG encephalomyelitis and NMDARE has been clinically identified. In these diseases, both MOG-Ab and NMDAR-Ab are positive. Previous studies were almost case reports and incomprehensive which focused on this kind of overlapping syndrome in adults. METHODS: We reported a rare case of MNOS. In addition, we reviewed the clinical characteristics, diagnosis, and treatment of MNOS in adults by consulting relevant literature. RESULTS: The patient initially presented with CNS demyelination symptoms followed by recurrent encephalitis, concomitant anti-MOG, and NMDAR antibodies. His symptoms improved significantly after initiating hormonal therapy. We searched previous MNOS case reports and 17 adult MNOS cases were retrieved. The previous history of all patients was unremarkable. Most of these patients (72.2%, 13/18) first developed NMDR encephalitis-related symptoms, such as cognitive behavior abnormalities, cognitive decline, and epilepsy. Some patients (16.7%, 3/18) first developed MOG-related demyelinating symptoms, such as visual deterioration, walking instability, and dizziness. The most common site of new brain lesions was the supratentorial region. In the acute phase, MNOS patients were sensitive to hormone therapy. During the follow-up, 72.2% (13/18) of the patients relapsed, with a median interval of 12.25 months. Immunotherapy was still effective after recurrence, and no deaths were reported. CONCLUSIONS: (1) The clinical manifestations of MNOS are atypical, sometimes like MOG encephalomyelitis, sometimes like NMDARE, sometimes both of the characteristic clinical manifestations are present. (2) Immunotherapy is the primary treatment of patients with MNOS. (3) MNOS are prone to recurrence, and serum MOG and tumor markers should be monitored.