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PURPOSE: This study aimed to develop a Quality of Life (QOL) assessment scale for older patients with Neuro-co-Cardiological Diseases (NCCD) and to evaluate the reliability and validity of the scale. METHOD: The study participants were derived from the Elderly Individuals with NCCD Registered Cohort Study (EINCCDRCS), a multicenter registry of patients with NCCD. The preliminary testing of the questionnaire was conducted among 10 older individuals aged 65 years and older who had NCCD and were recruited from the registry. Other patients who met the inclusion criteria participated in the field testing. After verifying the unidimensionality, local independence, and monotonicity assumptions of the scale, we employed the Rasch model within Item Response Theory framework to assess the quality of the scale through methods including internal consistency, criterion validity, Wright map, and item functioning differential. Subsequently, we assessed the construct validity of the scale by combining exploratory factor analysis with confirmatory factor analysis. RESULTS: Based on well-validated scales such as the short-form WHOQOL-OLD, HeartQOL, IQCODE, and SF-36, an original Neuro-co-Cardiological Diseases Quality of Life scale (NCCDQOL) was developed. 196 individuals from the EINCCDRCS were included in the study, with 10 participating in the preliminary testing and 186 in the field testing. Based on the results of the preliminary testing, the original questionnaire was refined through item deletion and adjustment, resulting in an 11-item NCCDQOL questionnaire. The Rasch analysis of the field testing data led to the removal of 21 misfitting individuals. The NCCDQOL demonstrated a four-category structure, achieved by combining two response categories. This structure aligned with the assumptions of unidimensionality, local independence, and monotonicity. The NCCDQOL also exhibited good validity and reliability. CONCLUSION: The revised NCCDQOL questionnaire demonstrated good reliability and validity in the Rasch model, indicating promising potential for clinical application.
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Calidad de Vida , Humanos , Calidad de Vida/psicología , Anciano , Masculino , Femenino , Encuestas y Cuestionarios/normas , Estudios de Cohortes , Anciano de 80 o más Años , Enfermedades del Sistema Nervioso/psicología , Enfermedades del Sistema Nervioso/diagnóstico , Cardiopatías/psicología , Cardiopatías/diagnóstico , Reproducibilidad de los Resultados , Sistema de Registros , ComorbilidadRESUMEN
Inflammatory myofibroblastic tumor (IMT) is a rare pathological entity first described in 1939. This lesion is most commonly found in the lungs, but cases involving other systems, such as the central nervous system known as intracranial IMT (IIMT), have also been reported. Diagnosis currently relies on pathological results due to the lack of characteristic imaging changes. Surgical resection is an effective treatment, though the disease is invasive and may recur. Previous literature has reported a high level of programmed death 1 (PD-1) expression in IMT tissues, suggesting that immunotherapy may be effective for this condition. In this case report, we present a middle-aged male who received PD-1 inhibitor and oncolytic adenovirus (Ad-TD-nsIL12) treatment after IIMT resection surgery. This successful approach provides a new direction for the treatment of IIMT.
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Adenoviridae , Neoplasias Encefálicas , Inhibidores de Puntos de Control Inmunológico , Viroterapia Oncolítica , Humanos , Masculino , Viroterapia Oncolítica/métodos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Encefálicas/terapia , Persona de Mediana Edad , Adenoviridae/genética , Virus Oncolíticos/genética , Antígeno B7-H1/antagonistas & inhibidores , Neoplasias de Tejido Muscular/terapia , Terapia Combinada , Resultado del TratamientoRESUMEN
AIMS: Gliomas are the most common central nervous system malignancies, with limited therapeutic options and poor prognosis, which are primarily attributed to the "immune desert" microenvironment. Previously, we constructed a three-gene-deleted oncolytic adenovirus (Ad-TD) loaded with non-secreting interleukin-12 (nsIL-12), which could be amplified in tumor cells and induce immunity to suppress tumors. However, the effects of this oncolytic virus on gliomas and their immune microenvironment remain unclear. There is an urgent need for further research. MATERIALS AND METHODS: We constructed a Syrian hamster brain tumor model and demonstrated the efficacy and mechanism of the novel oncolytic virus in treating brain tumors through a series of in vitro and in vivo experiments. We investigated the efficacy and safety (the number of hamsters in each group is either 5 or 10) of the oncolytic virus treatment in Syrian hamsters using a virus-treated group, a control virus-treated group, and a blank control group. KEY FINDINGS: In vitro assays showed that Ad-TD-nsIL-12 could specifically proliferate in brain tumor cells which induce tumor cell apoptosis and intracellular expression of interleukin (IL)-12. Moreover, in vivo experiments demonstrated that Ad-TD-nsIL-12 could effectively inhibit the progression of brain tumors and prolong survival. Ad-TD-nsIL-12 significantly enhanced T-cell infiltration in the brain tumor microenvironment. SIGNIFICANCE: Ad-TD-nsIL-12 can inhibit glioma progression and increase T-cell infiltration in the tumor tissue, particularly infiltration by cytotoxic T cells (CD8+). Ad-TD-nsIL-12 can amplify and produce IL-12, inducing anti-glioma immune responses to inhibit tumor progression.
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Neoplasias Encefálicas , Glioma , Viroterapia Oncolítica , Virus Oncolíticos , Cricetinae , Animales , Humanos , Virus Oncolíticos/genética , Interleucina-12/genética , Microambiente Tumoral , Línea Celular Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto , Glioma/terapia , Neoplasias Encefálicas/terapia , MesocricetusRESUMEN
The aim of the study was to investigate the incidence, prevalence and characteristics of multimorbidity in urban inpatients of different age groups. This study used data from the National Insurance Claim for Epidemiology Research (NICER) to calculate the overall incidence, prevalence, geographic and age distribution patterns, health care burden, and multimorbidity patterns for multimorbidity in 2017. According to our study, the overall prevalence of multimorbidity was 6.68%, and the overall prevalence was 14.87% in 2017. The prevalence of multimorbidity increases with age. The pattern of the geographic distribution of multimorbidity shows that the prevalence of multimorbidity is relatively high in South East China. The average annual health care expenditure of patients with multimorbidity increased with age and rose rapidly, especially among older patients. Patients with cancer and chronic kidney disease have higher treatment costs. Patients with hypertension or ischemic heart disease had a significantly higher relative risk of multimorbidity than other included noncommunicable diseases (NCDs). Hyperlipidemia has generated the highest number of association rules, which may suggest that hyperlipidemia may be both a risk factor for other NCDs and an outcome of them.
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Hiperlipidemias , Hipertensión , Humanos , Multimorbilidad , Prevalencia , Incidencia , Hipertensión/epidemiología , China/epidemiologíaRESUMEN
BACKGROUND: Based on the literature and data on its clinical trials, the incidence of venous thromboembolism (VTE) in patients undergoing neurosurgery has been 3.0%~26%. We used advanced machine learning techniques and statistical methods to provide a clinical prediction model for VTE after neurosurgery. METHODS: All patients (n = 5867) who underwent neurosurgery from the development and retrospective internal validation cohorts were obtained from May 2017 to April 2022 at the Department of Neurosurgery at the Sanbo Brain Hospital. The clinical and biomarker variables were divided into pre-, intra-, and postoperative. A univariate logistic regression (LR) was applied to explore the 67 candidate predictors with VTE. We used a multivariable logistic regression (MLR) to select all significant MLR variables of MLR to build the clinical risk prediction model. We used a random forest to calculate the importance of significant variables of MLR. In addition, we conducted prospective internal (n = 490) and external validation (n = 2301) for the model. RESULTS: Eight variables were selected for inclusion in the final clinical prediction model: D-dimer before surgery, activated partial thromboplastin time before neurosurgery, age, craniopharyngioma, duration of operation, disturbance of consciousness on the second day after surgery and high dose of mannitol, and highest D-dimer within 72 h after surgery. The area under the curve (AUC) values for the development, retrospective internal validation, and prospective internal validation cohorts were 0.78, 0.77, and 0.79, respectively. The external validation set had the highest AUC value of 0.85. CONCLUSIONS: This validated clinical prediction model, including eight clinical factors and biomarkers, predicted the risk of VTE following neurosurgery. Looking forward to further research exploring the standardization of clinical decision-making for primary VTE prevention based on this model.
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Background: Gliomas are the most commonly-detected malignant tumors of the brain. They contain abundant long non-coding RNAs (lncRNAs), which are valuable cancer biomarkers. LncRNAs may be involved in genomic instability; however, their specific role and mechanism in gliomas remains unclear. LncRNAs that are related to genomic instability have not been reported in gliomas. Methods: The transcriptome data from The Cancer Genome Atlas (TCGA) database were analyzed. The co-expression network of genomic instability-related lncRNAs and mRNA was established, and the model of genomic instability-related lncRNA was identified by univariate Cox regression and LASSO analyses. Based on the median risk score obtained in the training set, we divided the samples into high-risk and low-risk groups and proved the survival prediction ability of genomic instability-related lncRNA signatures. The results were verified in the external data set. Finally, a real-time quantitative polymerase chain reaction assay was performed to validate the signature. Results: The signatures of 17 lncRNAs (LINC01579, AL022344.1, AC025171.5, LINC01116, MIR155HG, AC131097.3, LINC00906, CYTOR, AC015540.1, SLC25A21.AS1, H19, AL133415.1, SNHG18, FOXD3.AS1, LINC02593, AL354919.2 and CRNDE) related to genomic instability were identified. In the internal data set and Gene Expression Omnibus (GEO) external data set, the low-risk group showed better survival than the high-risk group (P < 0.001). In addition, this feature was identified as an independent risk factor, showing its independent prognostic value with different clinical stratifications. The majority of patients in the low-risk group had isocitrate dehydrogenase 1 (IDH1) mutations. The expression levels of these lncRNAs were significantly higher in glioblastoma cell lines than in normal cells. Conclusions: Our study shows that the signature of 17 lncRNAs related to genomic instability has prognostic value for gliomas and could provide a potential therapeutic method for glioblastoma.
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Glioblastoma , Glioma , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , Pronóstico , Inestabilidad Genómica/genética , Mutación , Glioma/genéticaRESUMEN
Cuproptosis is a newly discovered form of cell death. It is regulated by a string of genes. The genes are identified to influence the tumor progression, but in glioma, the cuproptosis-related genes are little studied. The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) were used to screen for SLC31A1 gene expression in glioma and healthy tissue samples. The results were validated using the Gene Expression Omnibus (GEO) and quantitative real-time polymerase chain reaction (qPCR). The Human Protein Atlas (HPA) and the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) were used to validate our results at the protein level. Multivariable analysis and Kaplan-Meier survival curves were used to examine the relationship among SLC31A1 gene expression, clinical parameters, and survival rates. The online Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) was used to find the genes and proteins that correlate to SLC31A1. The immune infiltration analysis was performed using the Tumor Immune Estimation Resource (TIMER) databases. Small interfering RNA was used to knock down the SLC31A1 expression, and the cell proliferation, apoptosis, and migration were analyzed using cell counting kit-8, flow cytometry, and transwell. The glioma patients have higher SLC31A1 expression levels, which increase as the World Health Organization (WHO) grade escalates. The survival analysis illustrates that the SLC31A1 gene expression negatively correlates with overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS). The immune infiltration analysis shows the SLC31A1 gene positively correlates with T helper 2 (Th2) cells, macrophages, and M2-type macrophages and negatively correlates with plasmacytoid dendritic cells (pDCs), natural killer (NK) CD56bright cells, and CD8 T cells. The in vitro KD experiment shows the SLC31A1 knockdown depressed the glioma cell proliferation and migration and promoted the apoptosis rate. The SLC31A1 gene expression can shorten the survival time of glioma patients. In vitro study shows that SLC31A1 can promote cell proliferation, and migration, and depress the cell apoptosis of glioma cells. It also can promote the formation of a tumor-suppressive microenvironment.
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Apoptosis , Glioma , Proteómica , Humanos , Apoptosis/genética , Proliferación Celular , Transportador de Cobre 1 , Glioma/genética , Macrófagos , Microambiente Tumoral , CobreRESUMEN
Neurosurgeons often face this dilemma. Brain neoplasm patients undergoing neurosurgery are at a high risk of venous thrombosis. However, antithrombotic drugs may induce bleeding complications. Therefore, we compared the efficacy and safety of prophylaxis for venous thromboembolism (VTE) in brain neoplasm patients undergoing neurosurgery. We searched Cochrane Central Register of Controlled Trials, Ovid MEDLINE(R), and Embase from inception to January 2022 for randomized controlled trials (RCTs) comparing the prophylactic measures efficacy and safety for VTE in brain neoplasm patients undergoing neurosurgery. The main efficacy outcome was symptomatic or asymptomatic VTE. The safety outcomes included major bleeding, minor bleeding, all occurrences of bleeding, and all-cause mortality. We used (Log) odds ratio (OR) of various chemoprophylaxis regimens to judge the safety and effectiveness of VTE. Additionally, all types of intervention were ranked by the Surface Under the Cumulative Ranking (SUCRA) value. We included 10 RCTs with 1128 brain neoplasm patients undergoing neurosurgery. For symptomatic or asymptomatic VTE and proximal DVT or PE, DOACs, compared with placebo, can significantly reduce the events. DOACs were superior to all other interventions in the rank plot of these events. For major bleeding reduction, unfractionated heparin (SUCRA value = 0.21) demonstrated better safety efficacy than others. For minor bleeding reduction, DOACs had a significantly higher risk of minor bleeding compared with placebo [Log OR 16.76, 95% CrI (1.53, 61.13)], LMWH [Log OR 15.68, 95% CrI (0.26, 60.10)] and UFH [Log OR 15.93, 95% CrI (0.22, 60.16)] respectively. Except for placebo (SUCRA values of 0.13), UFH (SUCRA values of 0.37) depicted better safety efficacy than others. For all-cause mortality, we found UFH always had significantly lower all-cause mortality compared with low-molecular-weight heparin (LMWH) [Log OR = 14.17, 95% CrI (0.05, 48.35)]. UFH plus intermittent pneumatic compression (IPC) (SUCRA value of 0.12) displayed the best safety for all-cause mortality. In our study, DOACs were more effective as prophylaxis for VTE in brain neoplasm patients undergoing neurosurgery. Regarding the safety of prophylaxis for VTE, UFH of chemoprophylaxis consistently demonstrated better safety efficacy, involving either major bleeding, minor bleeding, bleeding, or all-cause mortality.
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Neoplasias Encefálicas , Neurocirugia , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/tratamiento farmacológico , Anticoagulantes/efectos adversos , Metaanálisis en Red , Heparina/efectos adversos , Heparina de Bajo-Peso-Molecular/uso terapéutico , Hemorragia/inducido químicamente , Hemorragia/tratamiento farmacológico , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/tratamiento farmacológicoRESUMEN
Glioblastoma (GBM) is one of the most aggressive primary malignant brain tumors. The major challenge is the lack of effective therapeutic drugs due to the blood-brain barrier (BBB) and tumor heterogeneity. Remdesivir (RDV), a new member of the nucleotide analog family, has previously been shown to have excellent antiviral effects and BBB penetration, and was predicted here to have anti-GBM effects. In vitro experiments, RDV significantly inhibited the growth of GBM cells, with IC50 values markedly lower than those of normal cell lines or the same cell lines treated with temozolomide. Moreover, in multiple mouse models, RDV not only distinctly inhibited the progression and improved the prognosis of GBM but also exhibited a promising biosafety profile, as manifested by the lack of significant body weight loss, liver or kidney dysfunction or organ structural damage after administration. Furthermore, we investigated the anti-GBM mechanism by RNA-seq and identified that RDV might induce apoptosis of GBM cells by enhancing endoplasmic reticulum (ER) stress and activating the PERK-mediated unfolded protein response. In conclusion, our results indicated that RDV might serve as a novel agent for GBM treatment by increasing ER stress and inducing apoptosis in GBM cells.
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Neoplasias Encefálicas , Glioblastoma , Ratones , Animales , Neoplasias Encefálicas/patología , Glioblastoma/patología , Estrés del Retículo Endoplásmico , Temozolomida , Respuesta de Proteína Desplegada , Apoptosis , Línea Celular TumoralRESUMEN
Background: Medulloblastoma (MB) is a malignant tumor associated with a poor prognosis in part due to a lack of effective detection methods. Extrachromosomal circular DNA (eccDNA) has been associated with multiple tumors. Nonetheless, little is currently known on eccDNA in MB. Methods: Genomic features of eccDNAs were identified in MB tissues and matched cerebrospinal fluid (CSF) and compared with corresponding normal samples using Circle map. The nucleotides on both sides of the eccDNAs' breakpoint were analyzed to understand the mechanisms of eccDNA formation. Bioinformatics analysis combined with the Gene Expression Omnibus (GEO) database identified features of eccDNA-related genes in MB. Lasso Cox regression model, univariate and multivariate Cox regression analysis, time-dependent ROC, and Kaplan-Meier curve were used to assess the potential diagnostic and prognostic value of the hub genes. Results: EccDNA was profiled in matched tumor and CSF samples from MB patients, and control, eccDNA-related genes enriched in MB were identified. The distribution of eccDNAs in the genome was closely related to gene density and the mechanism of eccDNA formation was evaluated. EccDNAs in CSF exhibited similar distribution with matched MB tissues but were differentially expressed between tumor and normal. Ten hub genes prominent in both the eccDNA dataset and the GEO database were selected to classify MB patients to either high- or low-risk groups, and a prognostic nomogram was thus established. Conclusions: This study provides preliminary evidence of the characteristics and formation mechanism of eccDNAs in MB and CSF. Importantly, eccDNA-associated hub genes in CSF could be used as diagnostic and prognostic biomarkers for MB.
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N6-methyladenosine (m6A) modification is the most abundant modification in long noncoding RNAs (lncRNAs). Current studies have shown that the abnormal expression of m6A-related genes is closely associated with the tumorigenesis and progression of glioma. However, the role of m6A-related lncRNAs in glioma development is still unclear. Herein, we screened 566 m6A-related lncRNAs in glioma from The Cancer Genome Atlas (TCGA) database. The expression pattern of these lncRNAs could cluster samples into two groups, in which various classical tumor-related functions and the tumor immune microenvironment were significantly different. Subsequently, a nine-factor m6A-related lncRNA prognostic signature (MLPS) was constructed by using a LASSO regression analysis in the training set and was validated in the test set and independent datasets. The AUC values of the MLPS were 0.881, 0.918 and 0.887 for 1-, 3- and 5-year survival in the training set, respectively, and 0.856, 0.916 and 0.909 for 1-, 3-, and 5-year survival in the test set, respectively. Stratification analyses of the MLPS illustrated its prognostic performance in gliomas with different characteristics. Correlation analyses showed that the infiltrations of monocytes and tumor-associated macrophages (TAMs) were significantly relevant to the risk score in the MLPS. Moreover, we detected the expression of four MLPS factors with defined sequences in glioma and normal cells by using RT-PCR. Afterwards, we investigated the functions of LNCTAM34A (one of the MLPS factors) in glioma cells, which have rarely been reported. Via in vitro experiments, LNCTAM34A was demonstrated to promote the proliferation, migration and epithelial-mesenchymal transition (EMT) of glioma cells. Overall, our study revealed the critical role of m6A-related lncRNAs in glioma and elucidated that LNCTAM34A could promote glioma proliferation, migration and EMT.
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Advancements in omics-based technologies over the past few years have led to the discovery of numerous biologically relevant peptides encoded by small open reading frames (smORFs) embedded in long noncoding RNA (lncRNA) transcripts (referred to as microproteins here) in a variety of species. However, the mechanisms and modes of action that underlie the roles of microproteins have yet to be fully characterized. Herein, we provide the first experimental evidence of abundant microproteins in extracellular vesicles (EVs) derived from glioma cancer cells, indicating that the EV-mediated transfer of microproteins may represent a novel mechanism for intercellular communication. Intriguingly, when examining human plasma, 48, 11 and 3 microproteins were identified from purified EVs, whole plasma and EV-free plasma, respectively, suggesting that circulating microproteins are primarily enriched in EVs. Most importantly, the preliminary data showed that the expression profile of EV microproteins in glioma patient diverged from the health donors, suggesting that the circulating microproteins in EVs might have potential diagnostic application in identifying patients with glioma.
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Vesículas Extracelulares/metabolismo , Péptidos/genética , Transporte de Proteínas , ARN Largo no Codificante , Proteínas Sanguíneas/metabolismo , Fraccionamiento Celular , Línea Celular Tumoral , Vesículas Extracelulares/genética , Glioma/sangre , Glioma/genética , Células HEK293 , Humanos , Péptidos/metabolismoRESUMEN
Glioma is the most common tumor with the worst prognosis in the central nervous system. Current studies showed that glucose metabolism could affect the malignant progression of tumors. However, the study on the dysregulation of glucose metabolism in glioma is still limited. Herein, we firstly screened 48 differentially expressed glucose metabolism-related genes (DE-GMGs) by comparing glioblastomas to low-grade gliomas. Then a glucose metabolism-related gene (GMG)-based model (PC, lactate dehydrogenase A (LDHA), glucuronidase beta (GUSB), galactosidase beta 1 (GLB1), galactose mutarotase (GALM), or fructose-bisphosphatase 1 (FBP1)) was constructed by a protein-protein interaction (PPI) network and Lasso regression. Thereinto, the high-risk group encountered a worse prognosis than the low-risk group, and the M2 macrophage was positively relevant to the risk score. Various classical tumor-related functions were enriched by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Since protein GALM was rarely studied in glioma, we detected high expression of GALM by western blot and immunohistochemistry in glioma tissues. And experiments in vitro showed that GALM could promote the epithelial-to-mesenchymal transition (EMT) process of glioma cells and could be regulated by TNFAIP3 in glioma cells. Overall, our study revealed the critical role of glucose metabolism in the prognosis of patients with glioma. Furthermore, we demonstrated that GALM was significantly related to the malignancy of glioma and could promote glioma cells' EMT process.
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Glioma is the most common primary tumor in the central nervous system (CNS) with the worst prognosis. Accurate pathological diagnosis has always been a challenge for optimal management of glioma. Promoter methylation is an important mechanism of epigenetic silencing tumor-suppressor genes and a potential biomarker for differential diagnosis and prognosis. Herein, using the cationic conjugated polymer (CCP)-based fluorescence resonance energy transfer (FRET) technique, we realized a highly sensitive detection of promoter methylation in clinical samples of minimal methylation degree (1.25%) and trace DNA quantity (10 ng/µL). Results for three glioma-related genes (MGMT, CDKN2A, and TERT) were combined in a diagnostic classifier to analyze the glioma-CpG island methylator phenotype (G-CIMP), which achieved a sensitivity of 80% at a maximum specificity of 100% for a glioma diagnosis. Kaplan-Meier survival curves and Pearson correlation analysis revealed that the prognosis of glioma patients with high G-CIMP scores (>5) was significantly better than those with low G-CIMP scores, especially in diffuse midline glioma and astrocytoma. This CCP-based FRET technique for determining G-CIMP status could provide patients with rapid and reasonably accurate diagnosis of glioma, as well as a valuable prognostic prediction that can guide individual treatment.
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ADN/análisis , Fluorenos/química , Glioma/diagnóstico , Polímeros/química , Regiones Promotoras Genéticas , Compuestos de Amonio Cuaternario/química , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Niño , Preescolar , Islas de CpG , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , ADN/química , ADN/genética , Metilación de ADN , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Diagnóstico Diferencial , Femenino , Transferencia Resonante de Energía de Fluorescencia , Glioma/genética , Glioma/mortalidad , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Telomerasa/genética , Proteínas Supresoras de Tumor/genética , Adulto JovenRESUMEN
ABSTRACT: Tumor-associated macrophages (TAMs) play a crucial role in the immune response to many malignancies, but the signaling pathways by which the glioma microenvironment cross-talk with TAMs are poorly understood. The aim of this study was to uncover the potential signaling pathways of the regulation of TAMs and identify candidate targets for therapeutic intervention of glioma through bioinformatics analysis.Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) datasets were used to download RNA-Seq data and microarray data of human glioma specimen. Differentially expressed genes (DEGs) between CD68-high samples and CD68-low samples were sorted. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the DEGs was conducted. Protein-protein interaction (PPI) network were formed to identify the hub genes.The prognostic value of TAMs in glioma patients was confirmed. A total of 477 specific DEGs were sorted. The signaling pathway was identified in pathway enrichment and the DEGs showed prominent representations of immune response networks in glioma. The hub genes including C3, IL6, ITGB2, PTAFR, TIMP1 and VAMP8 were identified form the PPI network and they were all correlated positively with the expression of CD68 and showed the excellent prognostic value in glioma patients.TAMs can be used as a good prognostic indicator in glioma patients. By analyzing comprehensive bioinformatics data, we uncovered the underlying signaling pathway of the DEGs between glioma patients with high and low expression level of CD68. Furthermore, the 6 hub genes identified were closely associated with TAMs in glioma microenvironment and need further investigation.
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Glioma/sangre , Glioma/genética , Macrófagos Asociados a Tumores/inmunología , Antígenos CD/análisis , Antígenos CD/sangre , Antígenos de Diferenciación Mielomonocítica/análisis , Antígenos de Diferenciación Mielomonocítica/sangre , Biología Computacional/métodos , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Glioma/patología , Humanos , Pronóstico , Transducción de Señal/genética , Microambiente Tumoral/inmunologíaRESUMEN
BACKGROUND: Over the last few years, great progress has been made in the development of key technologies to detect peripheral blood-based, tumor-specific biomarkers, such as circulating tumor cells (CTCs) and circulating cell free tumor DNA (ctDNA). Despite the considerable advances and their multiple clinical values, liquid biopsies are challenged by the very low concentrations of CTCs and ctDNA in blood samples. Additionally, blood biomarkers which were found using data-driven methods may only be effective in few datasets. METHODS: We firstly collected the genes which have expression correlations between blood and the other tissues/organs using Genotype-Tissue Expression (GTEx). Survival hazard genes and differential expression genes of each cancer type in The Cancer Genome Atlas (TCGA) were then selected by Cox regression model and Wilcoxon rank sum test, respectively. By combining the P values of two steps, several blood biomarkers can be inferred for each cancer type. After applying these potential blood biomarker sets to 13 datasets of blood samples from solid tumor patients using single sample gene set enrichment analyses (ssGSEA), we got an enrichment score (ES) for each sample. RESULTS: The inferred blood biomarker (BB infer) genes showed reliable predictive value in various malignancies. In all the blood samples that were analyzed, the ESs of positive BB Infer genes in cancer patients are higher than healthy people. Conversely, the ESs of negative BB Infer genes in cancer patients are lower than healthy people. Furthermore, lower ES of negative BB infer genes signify the dismal outcome of patients. CONCLUSIONS: We developed a novel solid tumor blood biomarker inference workflow for cancer screening and diagnosis. Moreover, we demonstrated the utility of this inference method in a series of blood sample datasets of solid tumor patients. These results suggested the potential value of this method in the screening, diagnosis and prognosis of cancers.
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Trochlear nerve cavernous hemangioma (CH) is a rare disease. There have been only five such cases reported in the world literature till date. The authors report a case of trochlear nerve CH in the Asian population and review the relevant literature. A 49-year-old Asian woman presented with gradually worsening double vision for 6 years. Physical examination identified a complete paralysis of left trochlear nerve. In imaging, a circular lesion measuring about 1 cm in diameter was found in the left ambient cistern. The lesion was completely excised through the left-side subtemporal approach, with a diagnosis of trochlear nerve CH confirmed by pathological examination. Further nerve anastomosis was not adopted, and the patient remained clinically stable in a two years' follow-up. This report provides more information about the history characteristics, imaging features, and surgical treatment strategies for trochlear nerve CH.
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Neoplasias de los Nervios Craneales , Hemangioma Cavernoso , Neoplasias de los Nervios Craneales/cirugía , Diplopía , Femenino , Hemangioma Cavernoso/diagnóstico por imagen , Hemangioma Cavernoso/cirugía , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos , Nervio TroclearRESUMEN
Glioblastoma (GBM) is one of the most common malignancies of the central nervous system, and the Isocitrate Dehydrogenase (IDH) mutation status of GBM has been recognized as a critical prognostic indicator. However, the molecular mechanism underlying the GBM with different IDH mutation status is still not unclear. In this study, a total of 353 DEGs including 207 up-regulated and 146 down-regulated were screened from multiple GBM data sets. Moreover, the biological processes and pathways enriched by DEGs were mainly associated with tumor progression, especially invasion and migration. Then, eight hub genes, including SDC4, SERPINE1, TNC, THBS1, COL1A1, CXCL8, TIMP1 and VEGFA, were selected from a PPI network. Finally, core genes, SERPINE1 and TIMP1, were identified from hub genes by survival analysis and sample validation. Overall, in this study, we revealed underlying molecular mechanisms in GBMs with different IDH mutation status and identified core genes that could be potential markers and targets for diagnosis and treatment of GBMs.
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Biomarcadores de Tumor/genética , Bases de Datos de Ácidos Nucleicos , Glioblastoma , Isocitrato Deshidrogenasa/genética , Mutación , Proteínas de Neoplasias/genética , Inhibidor 1 de Activador Plasminogénico/genética , Inhibidor Tisular de Metaloproteinasa-1/genética , Femenino , Glioblastoma/genética , Glioblastoma/mortalidad , Humanos , MasculinoRESUMEN
Diffuse glioma is the deadliest form of brain cancer, and the median survival of grade IV glioma (glioblastoma, GBM) is no more than 2 years even with maximal surgical resection followed by radiotherapy and chemotherapy, which are now the standard of care for GBM. Glioma shares common characteristics with most malignant tumours, such as invasiveness, rapid progression, resistance to various therapies and inevitable recurrence, while it also has its own unique features, such as high aggressiveness and immunotherapy resistance, which can be, respectively, attributed to epithelial-mesenchymal transition (EMT) and the immunosuppressive microenvironment. Here, we calculated the EMT score of glioma using The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA) and the Gene Expression Omnibus (GEO) datasets and validated its prognostic value. Then, we investigated its role in the glioma immune microenvironment, identified the enriched EMT-related immune genes and determined their specific biological functions in glioma. Furthermore, clinical relevance analysis showed the translational value of these EMT-related immune genes. In short, our findings reveal a critical link between EMT and the glioma immune microenvironment and offer important clues for further investigation of the underlying molecular mechanism.
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Biomarcadores de Tumor/genética , Neoplasias Encefálicas/genética , Transición Epitelial-Mesenquimal , Glioma/genética , Microambiente Tumoral/inmunología , Biomarcadores de Tumor/inmunología , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/patología , Glioma/inmunología , Glioma/patología , Humanos , Proteoma/genética , Proteoma/metabolismo , TranscriptomaRESUMEN
Glioblastoma (GBM) generally has a dismal prognosis, and it is associated with a poor quality of life as the disease progresses. However, the development of effective therapies for GBM has been deficient. Ubiquitin-conjugating enzyme E2T (UBE2T) is a member of the E2 family in the ubiquitin-proteasome pathway and a vital regulator of tumour progression, but its role in GBM is unclear. In this study, we aimed to clarify the role of UBE2T in GBM. Bioinformatics analysis identified UBE2T as an independent risk factor for gliomas. Immunohistochemistry was used to measure UBE2T expression in GBM and normal tissue samples obtained from patients with GBM. The effects of UBE2T on GBM cell invasion and migration were analysed using the Transwell assay. BALB/c nude mice were used for the in vivo assays. Immunoblotting and immunoprecipitation were performed to determine the molecular mechanisms. UBE2T was highly expressed in GBM tissues, and its expression was linked to a poor prognosis. In vitro, depletion of UBE2T significantly suppressed cell invasion and migration. Moreover, UBE2T depletion suppressed the growth of GBM subcutaneous tumours in vivo. Further experiments revealed that UBE2T suppressed invasion and migration by regulating epithelial- mesenchymal transition (EMT) via stabilising GRP78 in GBM cells. We uncovered a novel UBE2T/GRP78/EMT regulatory axis that modulates the malignant progression and recurrence of GBM, indicating that the axis might be a valuable therapeutic target.