Mitochondrial RNA modification-based signature to predict prognosis of lower grade glioma: a multi-omics exploration and verification study.

Mitochondrial RNA modification (MRM) plays a crucial role in regulating the expression of key mitochondrial genes and promoting tumor metastasis. Despite its significance, comprehensive studies on MRM in lower grade gliomas (LGGs) remain unknown. Single-cell RNA-seq data (GSE89567) was used to evaluate the distribution functional status, and correlation of MRM-related genes in different cell types of LGG microenvironment. We developed an MRM scoring system by selecting potential MRM-related genes using LASSO regression analysis and the Random Survival Forest algorithm, based on multiple bulk RNA-seq datasets from TCGA, CGGA, GSE16011, and E-MTAB-3892. Analysis was performed on prognostic and immunological features, signaling pathways, metabolism, somatic mutations and copy number variations (CNVs), treatment responses, and forecasting of potential small-molecule agents. A total of 35 MRM-related genes were selected from the literature. Differential expression analysis of 1120 normal brain tissues and 529 LGGs revealed that 22 and 10 genes were upregulated and downregulated, respectively. Most genes were associated with prognosis of LGG. METLL8, METLL2A, TRMT112, and METTL2B were extensively expressed in all cell types and different cell cycle of each cell type. Almost all cell types had clusters related to mitochondrial RNA processing, ribosome biogenesis, or oxidative phosphorylation. Cell-cell communication and Pearson correlation analyses indicated that MRM may promoting the development of microenvironment beneficial to malignant progression via modulating NCMA signaling pathway and ICP expression. A total of 11 and 9 MRM-related genes were observed by LASSO and the RSF algorithm, respectively, and finally 6 MRM-related genes were used to establish MRM scoring system (TRMT2B, TRMT11, METTL6, METTL8, TRMT6, and TRUB2). The six MRM-related genes were then validated by qPCR in glioma and normal tissues. MRM score can predict the malignant clinical characteristics, abundance of immune infiltration, gene variation, clinical outcome, the enrichment of signaling pathways and metabolism. In vitro experiments demonstrated that silencing METTL8 significantly curbs glioma cell proliferation and enhances apoptosis. Patients with a high MRM score showed a better response to immunotherapies and small-molecule agents such as arachidonyl trifluoromethyl ketone, MS.275, AH.6809, tacrolimus, and TTNPB. These novel insights into the biological impacts of MRM within the glioma microenvironment underscore its potential as a target for developing precise therapies, including immunotherapeutic approaches.

A novel DDIT3 activator dehydroevodiamine effectively inhibits tumor growth and tumor cell stemness in pancreatic cancer.

BACKGROUND: The existence of pancreatic cancer stem cells (PCSCs) results in limited survival benefits from current treatment options. There is a scarcity of effective agents for treating pancreatic cancer patients. Dehydroevodiamine (DeHE), a quinazoline alkaloid isolated from the traditional Chinese herb Evodiae fructus, exhibited potent inhibition of pancreatic ductal adenocarcinoma (PDAC) cell proliferation and tumor growth both in vitro and in vivo. METHODS: The cytotoxic effect of DeHE on PDAC cells was assessed using CCK-8 and colony formation assays. The antitumor efficacy of DeHE were appraised in human PANC-1 xenograft mouse model. Sphere formation assay and flow cytometry were employed to quantify the tumor stemness. RNA-Seq analysis, drug affinity responsive target stability assay (DARTS), and RNA interference transfection were conducted to elucidate potential signaling pathways. Western blotting and immunohistochemistry were utilized to assess protein expression levels. RESULTS: DeHE effectively inhibited PDAC cell proliferation and tumor growth in vitro and in vivo, and exhibited a better safety profile compared to the clinical drug gemcitabine (GEM). DeHE inhibited PCSCs, as evidenced by its suppression of self-renewal capabilities of PCSCs, reduced the proportion of ALDH+ cells and downregulated stemness-associated proteins (Nanog, Sox-2, and Oct-4) both in vitro and in vivo. Furthermore, there is potential involvement of DDIT3 and its downstream DDIT3/TRIB3/AKT/mTOR pathway in the suppression of stemness characteristics within DeHE-treated PDAC cells. Additionally, results from the DARTS assay indicated that DeHE interacts with DDIT3, safeguarding it against degradation mediated by pronase. Notably, the inhibitory capabilities of DeHE on PDAC cell proliferation and tumor stemness were partially restored by siDDIT3 or the AKT activator SC-79. CONCLUSION: In summary, our study has identified DeHE, a novel antitumor natural product, as an activator of DDIT3 with the ability to suppress the AKT/mTOR pathway. This pathway is intricately linked to tumor cell proliferation and stemness characteristics in PDAC. These findings suggest that DeHE holds potential as a promising candidate for the development of innovative anticancer therapeutics.

Advances in the antitumor mechanisms of tripartite motif-containing protein 3.

The tripartite motif-containing (TRIM) protein family has steadily become a hotspot in tumor-related research. As a member of the E3 ubiquitin ligase family, TRIM is working on many crucial biological processes, including the regulation of tumor cell proliferation, metastasis, apoptosis, and autophagy. Among the diverse TRIM superfamily members, TRIM3 operates via different mechanisms in various types of tumors. This review primarily focuses on the current state of research regarding the antitumor mechanisms of TRIM3 in different cancers. A more in-depth study of TRIM3 may provide new directions for future antitumor treatments. Our review focuses on TRIM3 proteins and cancer. We searched for relevant articles on the mechanisms by which TRIM3 affects tumorigenesis and development from 1997 to 2023 and summarized the latest progress and future directions. Triad-containing motif protein 3 (TRIM3) is an important protein, which plays a key role in the process of tumorigenesis and development. The comprehensive exploration of TRIM3 is anticipated to pave the way for future advancements in antitumor therapy, which is expected to be a new hallmark for cancer detection and a novel target for drug action. TRIM3 is poised to become a significant milestone in cancer detection and a promising focal point for drug intervention. Recent years have witnessed notable progress in research aimed at unraveling the antitumor mechanism of TRIM3, with far-reaching implications for practical tumor diagnosis, treatment protocols, efficacy evaluation, economics, and pharmaceutical utilization.

Effects of lead contamination on histology, antioxidant and intestinal microbiota responses in freshwater crayfish, Procambarus clarkii.

The red swamp crayfish (Procambarus clarkii) is an important farming species in China and there is a high degree of overlap between the main crayfish production areas and areas contaminated with the heavy metal lead (Pb), thus putting crayfish farming at potential risk of Pb contamination. To assess the toxic effects of Pb on crayfish, in this study they were exposed to different concentrations of Pb (0, 0.1, 1, 10, 50 mg/L) for 72 h, and 0.1 mg/L represents the level of Pb in the contaminated water. Histomorphology and activities of antioxidant or immune-related enzymes suggest that the damage of Pb to the hepatopancreas and intestine was dose- and time-dependent, with the intestine being more sensitive to Pb than the hepatopancreas. Notably, after a short period (24 h) of stress at low concentrations (0.1 mg/L) of Pb, the malondialdehyde (MDA) content and antioxidant enzymes such as catalase (CAT) and glutathione peroxidase (GSH-Px) in the intestine of crayfish showed significant changes, indicating that low concentrations of Pb were also highly detrimental to crayfish. High-throughput sequencing of the intestinal microbial community indicated that Pb exposure led to a disturbance in the relative abundance of intestinal bacteria, increasing the abundance of pathogenic bacteria (Bosea, Cloacibacterium, Legionella spp.) and decreasing the abundance of potentially beneficial bacteria (Chitinibacter, Chitinilyticum, Paracoccus, Microbacterium, Demequina, and Acinetobacter spp.). In conclusion, Pb damages the hepatopancreas and intestinal barrier of crayfish, leading to the destruction of their anti-stress ability and immune response, and at the same time disrupts the homeostasis of intestinal microbes, resulting in adverse effects on the gut. This study contributed to the assessment of the ecotoxicity of the heavy metal Pb to the crustacean aquatic animals.

Methyl cinnamate protects against dextran sulfate sodium-induced colitis in mice by inhibiting the MAPK signaling pathway.

Effective and non-toxic therapeutic agents are lacking for the prevention and treatment of colitis. Previous studies found that methyl cinnamate (MC), extracted from galangal ( Alpinia officinarum Hance), has anti-inflammatory properties. However, whether MC is effective as anti-colitis therapy remains unknown. In this study, we investigate the therapeutic effects of MC on dextran sulfate sodium (DSS)-induced colitis in mice and further explore its potential mechanism of action. MC treatment relieves symptoms associated with DSS-induced colitis, including the recovery of DSS-induced weight loss, decreases the disease activity index score, and increases the colon length without toxic side effects. MC treatment protects the integrity of the intestinal barrier in mice with DSS-induced colitis and inhibits the overexpression of pro-inflammatory cytokines in vivo and in vitro. Moreover, the MAPK signaling pathway is found to be closely related to the treatment with MC of colitis. Western blot analysis show that phosphorylation of the p38 protein in colon tissues treated with MC is markedly reduced and phosphorylation levels of the p38, JNK and ERK proteins are significantly decreased in RAW 264.7 cells treated with MC, indicating that the mechanism of MC in treating DSS-induced colitis could be achieved by inhibiting the MAPK signaling pathway. Furthermore, 16S RNA sequencing analysis show that MC can improve intestinal microbial dysbiosis in mice with DSS-induced colitis. Altogether, these findings suggest that MC may be a novel therapeutic candidate with anti-colitis efficacy. Furthermore, MC treatment relieves the symptoms of colitis by inhibiting the MAPK signaling pathway and improving the intestinal microbiota.

[Development and Evaluation of Prognostic Nomogram Model for Adult Ventricle Glioma Patients].

Objective: To explore the prognostic factors of adult ventricle glioma (AVG) and to construct and evaluate a survival-related prognostic nomogram model, which could provide further reference for the clinical management of AVG patients. Methods: The patients covered in the study were selected from the Surveillance Epidemiology and End Results (SEER) database (1973-2016). They all had definite histological diagnosis of AVG. They were assigned randomly to the training cohort and the validation cohort by random number table at a 2/1 ratio. Survival analysis was performed by Kaplan-Meier analysis. Cox regression analysis was employed to determine the independent prognostic factors for overall survival (OS) and cancer-specific survival (CSS). Then, integrating the basic characteristics of patients, the survival-related nomogram predictive model for OS and CSS in the training cohort was constructed, respectively. After that, internal cross validation and external validation of the model were carried out with the training cohort and the validation cohort in succession. The authenticity and reliability of the nomogram model were evaluated by calculating the concordance index (C-index). Calibration plots were constructed to assess the agreement between the predicted values and the observed values in the training cohort and the validation cohort. Results: A total of 369 AVG patients, including 218 males and 151 females, were included. The median age of the patients was 53. According to the WHO classification of gliomas, 66 (17.9%) patients had grade Ⅱ gliomas, 73 (19.8%) had grade Ⅲ gliomas, and 230 (62.3%) had grade Ⅳ gliomas. Regarding the extent of resection (EOR), 59 (16.0%) had gross total resection (GTR) and 145 (39.3%) had subtotal resection (STR) or partial resection (PR). Of all the patients, 167 (45.3%) received postoperative radiotherapy and 143 (38.8%) received postoperative chemotherapy. Patients were randomized into the training cohort ( n=246) and the validation cohort ( n=123), and there was no significant difference ( P>0.05) in the basic clinical characteristics between the training cohort and the validation cohort. In the training cohort, Cox regression analysis revealed that the independent prognostic factors for OS and CSS included age≥65, grades Ⅲ and Ⅳ according to the WHO classification of gliomas, and not receiving radiotherapy. Furthermore, 5 variables, including age, gender, WHO grades, surgery, and radiotherapy, were used to construct the nomogram model for predicting 6-month, 1-year, and 2-year OS and CSS. The results of internal cross validation in the training cohort showed that the C-indexes of OS and CSS were 0.758 and 0.765, respectively. The external validation results of the validation cohort showed that the C-indexes of OS and CSS were 0.733 and 0.719, respectively. Calibration plots for 6-month, 1-year, and 2-year OS in the training cohort showed relatively good agreement, while in the validation cohort the agreement was relatively low. The 6-month, 1-year, and 2-year CSS calibration plots had results similar to the calibration plots of OS. Conclusion: This nomogram predictive model of OS and CSS showed moderately reliable predictive performance, providing helpful reference information for clinicians to make quick and simple assessment of the survival probability of AVG patients.

Attenuated Toxoplasma gondii enhances the antitumor efficacy of anti-PD1 antibody by altering the tumor microenvironment in a pancreatic cancer mouse model.

PURPOSE: To investigate whether attenuated Toxoplasma is efficacious against solid tumors of pancreatic cancer and whether attenuated Toxoplasma improves the antitumor activity of αPD-1 antibody on pancreatic cancer. METHODS: The therapeutic effects of attenuated Toxoplasma NRTUA strain monotherapy and combination therapy of NRTUA with anti-PD-1 antibody on PDAC tumor volume and tumor weight of Pan02 tumor-bearing mice were investigated. We characterized the effects of combination therapy of NRTUA with anti-PD-1 antibody on tumor-infiltrating lymphocytes and tumor-specific IFN-γ by using immunohistochemistry, flow cytometry and ELISA. The antitumor mechanisms of combination therapy of NRTUA with anti-PD-1 antibody were investigated via depletion of CD8+ T cells and IL-12. RESULTS: NRTUA strain treatment inhibited tumor growth in a subcutaneous mouse model of PDAC through activating dendritic cells and increasing CD8+ T cell infiltration in the tumor microenvironment. More importantly, combination therapy of NRTUA with anti-PD-1 antibody elicited a significant antitumor immune response and synergistically controlled tumor growth in Pan02 tumor-bearing mice. Specifically, the combination treatment led to elevation of CD8+ T cell infiltration mediated by dendritic cell-secreted IL-12 and to tumor-specific IFN-γ production in the PDAC tumor microenvironment. Also, the combination treatment markedly reduced the immunosuppressive myeloid-derived suppressor cell population in PDAC mice. CONCLUSION: These findings could provide a novel immunotherapy approach to treating solid tumors of PDAC and overcoming resistance to anti-PD-1 agents in PDAC tumors.

Elevated GIGYF2 expression suppresses tumor migration and enhances sensitivity to temozolomide in malignant glioma.

Glioma is a common type of malignant and aggressive tumor in the brain. Despite progress on mechanistic studies, current understanding of the initiation and progression of glioma remains incomplete. GIGYF2 is a critical regulator in neural development and degeneration, however, its contribution in glioma is not yet elucidated. In this study, using an integrative approach spanning bioinformatic analysis and functional approaches, we explored the potential contribution of GIGYF2 in glioma. Bioinformatic data from public database and our cohort showed that GIGYF2 expression was closely associated with low glioma malignancy and better patient survival. Elevation of GIGYF2 expression impaired cell migration and enhanced temozolomide sensitivity of human glioma cells. We further establish its molecular mechanism by demonstrating that GIGYF2 inhibits MMP-9 mediated cell migration pathway and pro-survival AKT/Bax/Caspase-3 signaling. Our work identifies the suppressive role of GIGYF2 in gliomas, and clarifies the relationship between GIGYF2 expression and glioma malignancy, which may provide a potential target for future interventions.

Different materials of cranioplasty for patients undergoing decompressive craniectomy: A protocol for systematic review and network meta-analysis.

BACKGROUND: Cranioplasty is widely applied on patients who has undergone decompress craniectomy (DC) due to intractable increased intracranial pressure and the cranioplasty materials have been on the bleeding edge of biomolecular and material science. This systematic review and network meta-analysis (NMA) will be conducted to comprehensively evaluate the safety and efficacy of different cranial implants for patients with cranial defects due to various reasons. METHODS AND ANALYSIS: This protocol has been reported following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. The following electronic databases will be searched from the date of database establishment to September 1, 2020: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, VIP, and Wanfang. Randomized controlled trials and non-randomized prospective studies focus on cranial implants will be included. Quality assessment will be conducted using Cochrane Collaboration's tool or risk of bias in nonrandomized studies of interventions based on their study designs. The primary outcome will be postoperative early mortality and implant failure while various complications for secondary outcomes. Pairwise and network meta-analysis will be conducted using STATA V.14 (StataCorp, College Station, Texas, USA). Subgroup analyses and sensitivity analyses will be conducted to assess the robustness of the results. ETHICS AND DISSEMINATION: This systematic review does not require an ethics approval or the need to obtain informed consent. The results will be published in a peer-reviewed scientific journal. PROTOCOL REGISTRATION NUMBER: INPLASY 202110001.

Tertiary lymphoid structure stratifies glioma into three distinct tumor subtypes.

OBJECTIVE: Tertiary lymphoid structure (TLS), also known as ectopic lymphoid organs, are found in cancer, chronic inflammation, and autoimmune diseases. However, the heterogeneity of TLS in gliomas is unclear. Therefore, it is necessary to identify TLS differences and define TLS subtypes. METHODS: The TLS gene profile of 697 gliomas from The Cancer Genome Atlas (TCGA) was used for consensus clustering to identify robust clusters, and the reproducibility of the stratification method was assessed in Chinese Glioma Genome Atlas (CGGA) cohort1, CGGA_cohort2, and GSE16011. Analyses of clinical characteristics, immune infiltration, and potential biological functions were performed for each subtype. RESULTS: Three resulting clusters (A, B, and C) were identified based on consensus clustering on the gene expression profile of TLS genes. There was a significant prognostic difference among the clusters, with a shorter survival for C than B and A. In comparison with the A and B subtypes, the C subtype was significantly enriched in primary immunodeficiency, intestinal immune network for lgG production, antigen processing and presentation, natural killer cell-mediated cytotoxicity, complement and coagulation cascades, cytokine-cytokine receptor interaction, leukocyte transendothelial migration, and some immune-related diseases. The levels of 23 immune cell types were higher in the C subtype than in the A and B subtypes. Finally, we developed and validated a riskscore based on TLS subtypes with better performance of prognosis prediction. CONCLUSIONS: This study presents a new stratification method according to the TLS gene profile and highlights TLS heterogeneity in gliomas.

Prognostic Significance of Preoperative Albumin to Alkaline Phosphatase Ratio in Patients with Glioblastoma.

Objective: To explore the prognostic value of preoperative albumin to alkaline phosphatase ratio (AAPR) in patients with newly-diagnosed glioblastoma (GBM) and its association with clinical characteristics. Patients and methods: A retrospective analysis was carried out on patients with newly diagnosed GBM who had undergone operation at the Department of Neurosurgery at West China Hospital between June 1st 2016 to December 31st 2018. X-tile software was applied to determine the optimal cut-off values for AAPR, neutrophil to lymphocyte ratio (NLR), and albumin. Cox regression analyses were applied to evaluate the prognostic value of AAPR in GBM. PSM analysis was conducted to verify the results. Results: A total of 197 and 154 GBM patients were included in original cohort and PSM cohort respectively. The optimal cut-off value for AAPR, NLR, and albumin were 0.56, 4.55 and 42.2 g/L respectively. High AAPR was only significantly related to longer overall survival (OS) (p=0.010) in original cohort. In PSM cohort, no clinical variable was evidently related to the level of AAPR. AAPR was determined to be an independent prognostic indicator in both original cohort (HR=0.599, 95%CI 0.437-0.822, p=0.001) and PSM cohort (HR=0.649, 95%CI 0.459-0.918, p=0.015). Prognostic models including AAPR had better prognostic accuracy than that including albumin. Conclusion: Preoperative AAPR was determined to be an independent risk factor of prognosis in newly-diagnosed GBM patients, and its prognostic ability was stronger than albumin. And PSM analysis also validated the results.

High prevalence of developmental venous anomaly in adult patients with midline thalamic diffuse gliomas.

OBJECTIVE: This study aimed to assess the prevalence of developmental venous anomaly (DVA) in patients with thalamic glioma. Furthermore, we explored the association between DVA and some important biomarkers, such as IDH1 mutation, and H3K27M mutation. PATIENTS AND METHODS: Patients who received tumor resection in West China Hospital between August 2009 and October 2017 were enrolled. Propensity score matching was conducted based on a logistic regression model and 1:1 matching for case and control was used to generate a new cohort from patients with meningioma. Chi-square test, t-test, univariate and multivariate analyses were employed to assess the prevalence of DVA in thalamic glioma and meningioma and to identify risk factors associated with DVA. RESULTS: Ninety-nine patients with thalamic glioma were enrolled in the current study (male, n = 54; female, n = 45). The mean age was 42.9 ± 15.3 years old. We identified a higher prevalence of DVA in 99 patients with thalamic glioma when compared with 99 patients with meningioma (18.18% vs. 7.07%), which was slightly lower than the prevalence of DVA in glioma reported in previous studies. Furthermore, the distribution of gender, age, and tumor grade in DVA did not reach statistical significance. Chi-square test, univariate and multivariate analyses showed that IDH1 mutation, ATRX mutation, MGMT promoter methylation, p53 mutation, MMP9, EGFR, and Top II positive expression, TERT mutation, and H3K27M mutation were not associated with the development of DVA in thalamic glioma. CONCLUSION: A higher prevalence of DVA was found in thalamic glioma compared with meningioma.

Clinical Significance of Preoperative Fibrinogen to Albumin Ratio in Patients with Glioblastoma: A Singe Center Experience.

OBJECTIVE: To explore the prognostic value of preoperative fibrinogen to albumin ratio (FAR) in patients with glioblastoma (GBM) and its association with clinical characteristics. PATIENTS AND METHODS: A retrospective analysis was carried out on patients with newly diagnosed GBM who had undergone operation at the Department of Neurosurgery at West China Hospital between June 1st 2015 to June 31st 2018. Receiver operating characteristic (ROC) curves were performed to determine the optimal cut-off values for fibrinogen, albumin, neutrophil to lymphocyte ratio (NLR), and FAR by calculating the maximum Youden index. Kaplan-Meier curves and Cox regression analyses were applied to evaluate the prognostic value of FAR in GBM. Harrell concordance index (C-index) and Akaike information criterion (AIC) were calculated to compare different prognostic models. RESULTS: A total of 206 GBM patients were included in this research. The optimal cut-off value for fibrinogen, albumin, NLR, and FAR were 2.57, 42.4, 2.28, and 0.068 respectively. High FAR was significantly related to older age, KPS≤80, IDH-1 wildtype, presence of preoperative seizures, higher NLR, and tumor location. In Cox regression analyses, high FAR was significantly associated with poor prognosis. Prognostic models including FAR had the largest C-index and lowest AIC. CONCLUSION: FAR was determined to be an independent risk factor of prognosis in patients with newly-diagnosed GBM. And the prognostic predictive ability of FAR is stronger than fibrinogen and albumin.

Isolation and Characterization of Antibacterial Carotane Sesquiterpenes from Artemisia argyi Associated Endophytic Trichoderma virens QA-8.

Carotane sesquiterpenes are commonly found in plants but are infrequently reported in the fungal kingdom. Chemical investigation of Trichoderma virens QA-8, an endophytic fungus associated with the inner root tissue of the grown medicinal herb Artemisia argyi H. Lév. and Vaniot, resulted in the isolation and characterization of five new carotane sesquiterpenes trichocarotins I-M (1-5), which have diverse substitution patterns, and seven known related analogues (6-12). The structures of these compounds were established on the basis of a detailed interpretation of their NMR and mass spectroscopic data, and the structures including the relative and absolute configurations of compounds 1-3, 5, 9, and 10 were confirmed by X-ray crystallographic analysis. In the antibacterial assays, all isolates exhibited potent activity against Escherichia coli EMBLC-1, with MIC values ranging from 0.5 to 32 µg/mL, while 7ß-hydroxy CAF-603 (7) strongly inhibited Micrococcus luteus QDIO-3 (MIC = 0.5 µg/mL). Structure-activity relationships of these compounds were discussed. The results from this study demonstrate that the endophytic fungus T. virens QA-8 from the planted medicinal herb A. argyi is a rich source of antibacterial carotane sesquiterpenes, and some of them might be interesting for further study to be developed as novel antibacterial agents.

Clinicopathological characteristics and treatment outcomes of epithelioid glioblastoma.

Epithelioid glioblastoma is a new variant of glioblastoma that has been recently recognized in the 2016 WHO classification of brain tumors. Given the rarity of epithelioid glioblastoma, the clinical characteristics, pathological features, radiological findings, and treatment outcomes are still not well characterized. Therefore, we identified eighty-four epithelioid glioblastoma cases to investigate these characteristics and identify the possible prognostic factors of survival. There were 55 male and 29 female patients with a mean age of 33.6 years. Headache (77.3%) was the most common clinical symptom, and other common symptoms included nausea or vomiting (34%), dizziness (20.5%), seizures (13.6%), and limb weakness (13.6%). Most lesions (88.1%) were located in cerebral lobes, especially in the frontal lobe and temporal lobe. One hundred percent of the patients were IDH1 wild-type (75/75) and INI-1 positive (58/58), and 57.3% (47/82) of patients harbored BRAFV600E mutation. The median overall survival (OS) of all patients was 10.5 months. Patients who received chemotherapy (p = 0.006) or radiotherapy (p = 0.022) had a longer survival than patients who did not. In addition, the K-M curve showed that the BRAFV600E mutation status was not associated with survival (p = 0.724). These findings may assist clinicians with better understanding and management of epithelioid glioblastoma.

Inhibition of mitochondrial carrier homolog 2 (MTCH2) suppresses tumor invasion and enhances sensitivity to temozolomide in malignant glioma.

BACKGROUND: Malignant glioma exerts a metabolic shift from oxidative phosphorylation (OXPHOs) to aerobic glycolysis, with suppressed mitochondrial functions. This phenomenon offers a proliferation advantage to tumor cells and decrease mitochondria-dependent cell death. However, the underlying mechanism for mitochondrial dysfunction in glioma is not well elucidated. MTCH2 is a mitochondrial outer membrane protein that regulates mitochondrial metabolism and related cell death. This study aims to clarify the role of MTCH2 in glioma. METHODS: Bioinformatic analysis from TCGA and CGGA databases were used to investigate the association of MTCH2 with glioma malignancy and clinical significance. The expression of MTCH2 was verified from clinical specimens using real-time PCR and western blots in our cohorts. siRNA-mediated MTCH2 knockdown were used to assess the biological functions of MTCH2 in glioma progression, including cell invasion and temozolomide-induced cell death. Biochemical investigations of mitochondrial and cellular signaling alternations were performed to detect the mechanism by which MTCH2 regulates glioma malignancy. RESULTS: Bioinformatic data from public database and our cohort showed that MTCH2 expression was closely associated with glioma malignancy and poor patient survival. Silencing of MTCH2 expression impaired cell migration/invasion and enhanced temozolomide sensitivity of human glioma cells. Mechanistically, MTCH2 knockdown may increase mitochondrial OXPHOs and thus oxidative damage, decreased migration/invasion pathways, and repressed pro-survival AKT signaling. CONCLUSION: Our work establishes the relationship between MTCH2 expression and glioma malignancy, and provides a potential target for future interventions.

Prognostic Significance and Gene Co-Expression Network of PLAU and PLAUR in Gliomas.

The urokinase-type plasminogen activator(PLAU) and its receptor PLAUR participate in a series of cell physiological activities on the extracellular surface. Abnormal expression of PLAU and PLAUR is associated with tumorigenesis. This study aims to evaluate the prognostic value of PLAU/PLAUR transcription expression in glioma and to explore how they affect the generation and progression of glioma. In this study, online databases are applied, such as Oncomine, GEPIA, CGGA, cBioPortal, and LinkedOmics. Overexpression of PLAU/PLAUR was found to be significantly associated with clinical variables including age, tumor type, WHO grade, histology, IDH-1 mutation, and 1p19q status. PLAU and PLAUR had a high correlation in transcriptional expression levels. High expression of PLAU and PLAUR predicted a poor prognosis in primary glioma and recurrent glioma patients, especially in lower grade gliomas. Cox regression analysis indicated that high expression of PLAU and PLAUR were independent prognostic factors for shorter overall survival in glioma patients. In gene co-expression network analysis PLAU and PLAUR and their co-expression genes were found to be involved in inflammatory activities and tumor-related signaling pathways. In conclusion, PLAU and PLAUR could be promising prognostic biomarkers and potential therapeutic targets of glioma patients.