Influence of SLC40A1 on Cytokine Interactions and Immune Infiltration in Glioblastoma.

Numerous studies have explored the various functions of Slc40a1 in cancer development. However, the role of Slc40a1 in primary glioblastoma requires further investigation. Initially, we observed that GBM patients with high Slc40a1 expression had a more favorable prognosis than those with low Slc40a1 expression, as evidenced by an analysis of the TIMER database. Subsequent analysis using the cancer genome atlas (TCGA) database enabled us to identify potential underlying mechanisms involved. Further analyses, including GO, KEGG, GSEA, immune infiltration, and correlation analyses, revealed that Slc40a1 primarily affected cytokine interactions, particularly with Ccl14 and Il18, resulting in changes in the immune microenvironment and ultimately leading to a better prognosis in GBM patients. We validated our findings by examining a tissue microarray with 180 samples and confirmed that GBM patients with high SLC40A1 protein expression exhibited more favorable prognostic outcomes than those with low SLC40A1 protein expression. Immunofluorescence analysis also revealed a significant correlation between SLC40A1 protein expression and the protein expression of IL18 and CCL14. These findings suggest that Slc40a1 may play a role in GBM pathogenesis by modulating the tumor immune microenvironment through the regulation of Il18 and Ccl14. Hence, targeting Slc40a1 might offer potential benefits for immunotherapeutic interventions and prognostic assessments in GBM patients.

Prognosis and Immune Landscapes in Glioblastoma Based on Gene-Signature Related to Reactive-Oxygen-Species.

Glioblastoma (GBM) is the most malignant and aggressive primary brain tumor and is highly resistant to current therapeutic strategies. Previous studies have demonstrated that reactive oxygen species (ROS) play an important role in the regulation of signal transduction and immunosuppressive environment in GBM. To further study the role of ROS in prognosis, tumor micro-environment (TME) and immunotherapeutic response in GBM, an ROS-related nine-gene signature was constructed using the Lasso-Cox regression method and validated using three other datasets in our research, based on the hallmark ROS-pathway-related gene sets and the Cancer Genome Atlas GBM dataset. Differences in prognosis, TME scores, immune cell infiltration, immune checkpoint expression levels, and drug sensitivity between high-risk and low-risk subgroups were analyzed using R software. Collectively, our research uncovered a novel ROS-related prognostic model for primary GBM, which could prove to be a potential tool for clinical diagnosis of GBM, and help assess the immune and molecular characteristics of ROS in the tumorigenesis and immunosuppression of GBM. Our research also revealed that the expressions of ROS-related genes-HSPB1, LSP1, and PTX3-were closely related to the cell markers of tumor-associated macrophages (TAMs) and M2 macrophages validated by quantitative RT-PCR, suggesting them could be potential targets of immunotherapy for GBM.

A novel lncRNA-LINC01116 regulates tumorigenesis of glioma by targeting VEGFA.

Brain glioma is the most common malignant tumor of the central nervous system, and one of the leading causes of death in patients with intracranial tumors. The clinical outcome of glioma is usually poor due to abundant vascularity, fast growth and susceptibility of invasion to normal brain tissues. Our microarray study showed that lncRNA-LINC01116 was significantly upregulated in glioma tissues and played an important role in cell proliferation, cycle, migration, invasion and angiogenesis. In addition, vascular endothelial growth factor (VEGFA) may be the major target genes in the downstream of lncRNA-LINC01116. Dual luciferase assay showed that LINC01116 and VEGFA both contained a miR-31-5p binding site, and LINC01116 could regulate the expression of VEGFA through competitive absorption of miR-31-5p. RNA immunoprecipitation indicated that LINC01116 and VEGFA were present in the miR-31-5p-RISC complex, and biotinylated miR-31-5p pull-down assay suggested that there was a competitive relationship between LINC01116 and VEGFA to bind with miR-31-5p. Collectively, our study has identified a novel lncRNA-LINC01116 and clarified the role and mechanism of LINC01116 in the tumorigenesis of glioma. LINC01116 may prove to be a potential target for the clinical diagnosis and treatment of glioma.

Differential Expression of Circular RNAs in Glioblastoma Multiforme and Its Correlation with Prognosis.

OBJECTIVE: The present study aimed to explore the expression profiles of circular RNAs (circRNAs) in glioblastoma multiforme (GBM) in an attempt to identify potential core genes in the pathogenesis of this tumor. METHODS: Differentially expressed circRNAs were screened between tumor tissues from five GBM patients and five normal brain samples using Illumina Hiseq. Bioinformatics analysis was used to analyze their potential function. CircBRAF was further detected in different WHO grades glioma tissues and normal brain tissues. Kaplan-Meier curves and multivariate Cox's analysis were used to analyze the association between circBRAF expression level and prognosis of glioma patients. RESULTS: A total of 1411 differentially expressed circRNAs were identified in GBM patients including 206 upregulated circRNAs and 1205 downregulated circRNAs. Differential expression of circRNAs was closely associated with the biological process and molecular function. The downregulated circRNAs were mainly associated with ErbB and Neurotrophin signaling pathways. Moreover, the expression level of circBRAF in normal brain tissues was significantly higher than that in glioma tissues (P<.001). CircBRAF was significantly lower in glioma patients with high pathological grade (WHO III & IV) than those with low grade (WHO I & II) (P<.001). Cox analysis revealed that high circBRAF expression was an independent biomarker for predicting good progression-free survival and overall survival in glioma patients (HR=0.413, 95% CI 0.201-0.849; HR=0.299, 95% CI 0.135-0.661; respectively). CONCLUSION: The present study identified a profile of dysregulated circRNAs in GBM. Bioinformatics analysis showed that dysregulated circRNAs might be associated with tumorigenesis and development of GBM. In addition, circBRAF could severe as a biomarker for predicting pathological grade and prognosis in glioma patients.

Clinical features and prognostic factors of WHO II and III adult spinal meningiomas: analysis of 25 cases in a single center.

Spinal World Health Organization (WHO) II and III meningiomas are relatively rare, and often associated with great clinical aggressiveness and poor overall survival. There are controversies over factors affecting the prognosis of this disease. The aim of this retrospective study was to evaluate factors that may affect the therapeutic outcome and prognosis of adult high-grade spinal meningiomas by reviewing the medical records of 25 patients who were surgically treated in our hospital between 2001 and 2014. Univariate and multivariate analyses were performed to identify prognostic variables relative to patient and tumor characteristics, and treatment modalities. All 25 patients (14 men and 11 women; mean age 46.6 ± 16.1 years) underwent surgical resection. Local recurrence was occurred in 13 (52.0 %) patients, and 10 (40.0 %) patients died during the follow-up periods. The 5-year recurrence rate was 60.0 % and the 5-year survival rate was 68.0 %. The results of statistical analysis suggested that Simpson resection grade and the number of involved segments were prognostic factors related to progression-free survival and that sex, age, preoperative Frankel score, the number of involved segments and WHO grade were closely correlated with survival. Furthermore, we confirmed that the number of involved segments was the major independent factor affecting recurrence of patients with adult spinal high-grade meningiomas, and that sex, age and WHO grade were prognostic factors affecting survival but not recurrence.

Analysis on therapeutic outcomes and prognostic factors of intracranial ependymoma: a report of 49 clinical cases in a single center.

Although intracranial ependymoma is relatively rare, it is often associated with great clinical aggressiveness and poor overall survival. There are controversies over factors affecting the prognosis of the disease. The aim of this retrospective study was to evaluate factors that may affect the therapeutic outcome and prognosis of intracranial ependymoma by reviewing the medical records of 49 patients who were surgically treated in our hospital between 2001 and 2014. Univariate and multivariate analyses were performed to identify prognostic variables relative to patient and tumor characteristics, and treatment modalities. All 49 patients (24 men and 25 women; mean age 27.6 years) underwent surgical resection, of whom 14 patients also underwent postoperative radiotherapy. Local recurrence was found in 15 (48.8 %) patients, and 22 (51.2 %) patients died during the follow-up periods. The 5-year recurrence rate was 65 % and the survival rate was 51 %. The results of statistical analysis suggested that preoperative extraventricular drainage and surgical resection extent were prognostic factors related to progression-free survival, and that age, surgical resection extent and histological grade were closely associated with survival. Interestingly, there was a significant correlation between the symptom of hydrocephalus and age (P = 0.010), and patients with a better clinical status (KPS ≥ 80) were significantly associated with a lower WHO grade (P = 0.007). In conclusion, we confirmed that surgical resection extent was the major independent factor affecting both recurrence and survival of patients with intracranial ependymoma, while age and WHO grade were prognostic factors affecting survival but not recurrence.

An integrative analysis of treatment, outcomes and prognostic factors for primary spinal anaplastic ependymomas.

The aim of this study was to elucidate the role of treatment modalities in primary spinal anaplastic ependymomas (PSAE) and identify promising prognostic factors. PSAE are rare tumors of the central nervous system with poorly understood clinical characteristics and treatment outcomes. We reviewed the literature in PubMed, Web of Science and Scopus databases to identify patients with PSAE. Multivariate Cox proportional hazards analysis and univariate Kaplan-Meier analysis were performed on the PSAE patients and overall survival (OS) and progression-free survival (PFS) were assessed to evaluate the clinical outcomes. Of the 40 patients with PSAE, the tumors were mostly intramedullary (n=19; 47.5%) and frequently involved the thoracic cord (n=25; 62.5%). Eighteen patients suffered recurrence during the follow-up with a median PFS of 24 months. The 1, 2, and 5year OS rates of the PSAE patients were 91.5%, 82.1%, and 63.1%, respectively. Gross total resection (GTR) was independently associated with prolonged PFS (hazard ratio [HR] 0.11; p=0.004) and OS (HR 0.11; p=0.003) in the multivariate analysis. Adjuvant radiotherapy also conferred improved PFS (HR 0.15; p=0.008) and OS (HR 0.16; p=0.022). Age, sex, tumor location and chemotherapy did not influence the outcomes in this group. The results of our study suggest that GTR and adjuvant radiotherapy are strong prognostic indicators in patients with PSAE and the role of chemotherapy is yet to be defined.

DNA repair gene XRCC3 Thr241Met polymorphism and glioma risk: a meta-analysis.

BACKGROUND: The polymorphism of XRCC3 Thr241Met has been indicated to be correlated with glioma susceptibility, but study results are still debatable. The present meta-analysis was performed to investigate the association between XRCC3 Thr241Met polymorphism and glioma. METHODS: A total of 3754 glioma patients and 4849 controls from nine separate studies were involved. The pooled odds ratio (OR) and its corresponding 95% confidence interval (CI) was assessed by the random-effects model. RESULTS: The association between XRCC3 Thr241Met polymorphism and glioma was significant in the recessive model (OR = 1.36; 95% CI, 1.02 - 1.82; P = 0.03). In a stratified analysis by the ethnicity, significantly increased risk was detected in Asians (OR = 1.93; 95% CI, 1.18 - 3.17; P = 0.009). CONCLUSIONS: In conclusion, XRCC3 Thr241Met polymorphism was implied to be associated with increased glioma risk. More studies are needed to validate this result.