CKAP2L, as an Independent Risk Factor, Closely Related to the Prognosis of Glioma.
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ABSTRACT:
SUBMITTER: Zhu L
PROVIDER: S-EPMC8494202 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundXRCC2, a homologous recombination-related gene, has been reported to be associated with a variety of cancers. However, its role in glioma has not been reported. This study aimed to find out the role of XRCC2 in glioma and reveal in which glioma-specific biological processes is XRCC2 involved based on thousands of glioma samples, thereby, providing a new perspective in the treatment and prognostic evaluation of glioma.MethodsThe expression characteristics of XRCC2 in thousands of glioma samples from CGGA and TCGA databases were comprehensively analyzed. Wilcox or Kruskal test was used to analyze the expression pattern of XRCC2 in gliomas with different clinical and molecular features. The effect of XRCC2 on the prognosis of glioma patients was explored by Kaplan-Meier and Cox regression. Gene set enrichment analysis (GSEA) revealed the possible cellular mechanisms involved in XRCC2 in glioma. Connectivity map (CMap) was used to screen small molecule drugs targeting XRCC2 and the expression levels of XRCC2 were verified in glioma cells and tissues by RT-qPCR and immunohistochemical staining.ResultsWe found the overexpression of XRCC2 in glioma. Moreover, the overexpressed XRCC2 was associated with a variety of clinical features related to prognosis. Cox and meta-analyses showed that XRCC2 is an independent risk factor for the poor prognosis of glioma. Furthermore, the results of GSEA indicated that overexpressed XRCC2 could promote malignant progression through involved signaling pathways, such as in the cell cycle. Finally, doxazosin, quinostatin, canavanine, and chrysin were identified to exert anti-glioma effects by targeting XRCC2.ConclusionsThis study analyzed the expression pattern of XRCC2 in gliomas and its relationship with prognosis using multiple datasets. This is the first study to show that XRCC2, a novel oncogene, is significantly overexpressed in glioma and can lead to poor prognosis in glioma patients. XRCC2 could serve as a new biomarker for glioma diagnosis, treatment, and prognosis evaluation, thus bringing new insight into the management of glioma.
| S-EPMC8164800 | biostudies-literature
Project description:AimsImmune checkpoint blockade has made breakthroughs in immunotherapy for glioma. However, current immunotherapy has therapeutic benefits only in a subset of patients and accompanied by immune-related side effects. SLAMF8 is a costimulatory molecule that affects the activation of macrophages in inflammation. The study of SLAMF8 may provide new information for immunological research and treatment of glioma.MethodsCGGA and TCGA cohorts of 946 patients with RNA sequencing data and full clinical information were analyzed using R language and GraphPad Prism 7.ResultsSLAMF8 was overexpressed along with malignancy progression and was a biomarker of mesenchymal subtype. As an independent prognostic factor, high SLAMF8 conferred reduced overall survival and chemotherapy resistance. SLAMF8 implied lower proportion of cancer cells along with increasing enrichment of monocytic lineage, myeloid dendritic cells. Functional analysis showed higher SLAMF8 indicated activation of antigen processing and presenting and the IFN-γ/TNF/TLR-mediated signaling. Meanwhile, coexpressing with classical checkpoint SLAMF8 aggravated immunosuppression and enhanced inflammation response.ConclusionOur study highlighted the important role of SLAMF8 in malignancy progression, shortened survival, and immune disorders. Further research on SLAMF8 in immunosuppression and inflammation response to glioma cells could aid immunotherapy for glioma.
| S-EPMC6488888 | biostudies-literature
Project description:In recent years, studies have revealed HOXA2 as a new oncogene, but its function is unknown in gliomas. We aimed to reveal the relationship between HOXA2 and glioma based on the Chinese Glioma Genome Atlas(CGGA) and the cancer genome atlas (TCGA). HOXA2 expression data and clinically relevant information of glioma patients were obtained from the CGGA and TCGA containing 1447 glioma tissues and five non-tumor brain tissues. The Wilcox or Kruskal tests were used to detect the correlation between the HOXA2 expression level and clinical data of glioma patients. the Kaplan-Meier method were used to examine the relationship between HOXA2 and overall patient survival. Gene set enrichment analysis (GSEA) was conducted to indirectly reveal the signaling pathways involved in HOXA2, and RT-PCR was used to detect HOXA2 expression in gliomas and non-tumor brain tissues. High HOXA2 expression was found to be positively correlated with clinical grade, histological type, age, and tumor recurrence, but negatively correlated with 1p19 codeletion and isocitrate dehydrogenase mutation status.RT-PCR results showed that HOXA2 expression levels were significantly higher in tumor tissues than in non-tumor brain tissues. GSEA showed that HOXA2 promoted the activation of the activation of the JAK-STAT-signaling pathway, focal adhesion, cell-adhesion-molecules-CAMS pathway, cytosolic DNA sensing pathway, and natural killer cell-mediated cytotoxicity. This study revealed for the first time that the novel oncogene,HOXA2, leads to poor prognosis in gliomas, and can be used as a biomarker for the diagnosis and treatment of gliomas.
| S-EPMC7469623 | biostudies-literature
Project description:ObjectiveDespite several clinicopathological factors being integrated as prognostic biomarkers, the individual variants and risk stratification have not been fully elucidated in lower grade glioma (LGG). With the prevalence of gene expression profiling in LGG, and based on the critical role of the immune microenvironment, the aim of our study was to develop an immune-related signature for risk stratification and prognosis prediction in LGG.MethodsRNA-sequencing data from The Cancer Genome Atlas (TCGA), Genome Tissue Expression (GTEx), and Chinese Glioma Genome Atlas (CGGA) were used. Immune-related genes were obtained from the Immunology Database and Analysis Portal (ImmPort). Univariate, multivariate cox regression, and Lasso regression were employed to identify differentially expressed immune-related genes (DEGs) and establish the signature. A nomogram was constructed, and its performance was evaluated by Harrell's concordance index (C-index), receiver operating characteristic (ROC), and calibration curves. Relationships between the risk score and tumor-infiltrating immune cell abundances were evaluated using CIBERSORTx and TIMER.ResultsNoted, 277 immune-related DEGs were identified. Consecutively, 6 immune genes (CANX, HSPA1B, KLRC2, PSMC6, RFXAP, and TAP1) were identified as risk signature and Kaplan-Meier curve, ROC curve, and risk plot verified its performance in TCGA and CGGA datasets. Univariate and multivariate Cox regression indicated that the risk group was an independent predictor in primary LGG. The prognostic signature showed fair accuracy for 3- and 5-year overall survival in both internal (TCGA) and external (CGGA) validation cohorts. However, predictive performance was poor in the recurrent LGG cohort. The CIBERSORTx algorithm revealed that naïve CD4+ T cells were significant higher in low-risk group. Conversely, the infiltration levels of M1-type macrophages, M2-type macrophages, and CD8+T cells were significant higher in high-risk group in both TCGA and CGGA cohorts.ConclusionThe present study constructed a robust six immune-related gene signature and established a prognostic nomogram effective in risk stratification and prediction of overall survival in primary LGG.
| S-EPMC7174786 | biostudies-literature
Project description:Glioma, a common malignant tumor of the central nervous system, has high invasiveness. The objective of the present study was to identify genes playing an important role in the development of glioma and to reveal their potential research value. Conjoint analysis on the GSE16011 dataset in the Gene Expression Omnibus (GEO) database and the 'Messenger RNA Expression Microarray of Diffuse Gliomas and Controls' dataset and 'RNA sequencing of Diffuse Gliomas' dataset in the Chinese Glioma Genome Atlas (CGGA) database is carried out in the study. The weighted correlation network analysis (WGCNA) was used to carry out co-expression analysis on the GSE16011. Finally, 24 genes significantly related to grade and prognosis were obtained. In addition, there is no report about CACNG2, JPH3, TUBB6 (tubulin β 6 class V), NRSN1, FAM19A2, NALCN, CDH18, GNAL on glioma.
| S-EPMC7253401 | biostudies-literature
Project description:Glioma is the most common malignant primary brain tumour. It is of great significance for the prognosis and personalized treatment of glioma patients to accurate identification of glioma based on biomarkers. Pyroptosis, a kind of programmed cell death, is closely related to tumour progression and tumour immune microenvironment. However, the role of pyroptosis in glioma remained unclear. Herein, we used glioma clinical and expression data from TCGA and CGGA to explore the relationship between pyroptosis and glioma. We first summarized the incidence of copy number variations and somatic mutations of 33 pyroptosis-related genes and explored prognostic correlation of these genes. Based on pyroptosis-related genes, three molecular subgroups of glioma related to prognosis were identified. We also found that each subgroup has unique immune and biological behaviours characteristics. Finally, based on 7 pyroptosis-related genes (CASP3, CASP4, CASP6, CASP8, CASP9, PRKACA and ELANE), we constructed a prognosis model by Lasso and Cox regression, which had a strong predictive power for the overall survival in CGGA test cohort (p < 0.05). In summary, we explored the role of pyroptosis-related genes in gliomas and the association of these genes with tumour immunity. We found the biomarkers valuable to diagnosis and prognosis, hence, provide reference to the development and treatment of tumorigenesis in glioma.
| S-EPMC8742236 | biostudies-literature
Project description:Gamma-interferon-inducible lysosomal thiol reductase, the only known lysosomal thiol reductase, is encoded by gene IFI30 and expressed constitutively in antigen-presenting cells. Our comprehensive study on IFI30 in gliomas found its expression to be high in glioblastomas and in gliomas with a mesenchymal subtype or wild-type isocitrate dehydrogenase, all of which indicated the malignancy and poor outcomes of gliomas. Kaplan-Meier survival analysis ascertained that high IFI30 expression conferred poor outcomes. The IFI30 expression levels also showed high efficiency in predicting 1-, 3- and 5-year overall survival. Univariable and multivariable Cox regression analyses were performed to define IFI30 as an independent prognostic marker. Biological process analysis suggested that IFI30 was involved in immune responses. ESTIMATE and CIBERSORT were applied to evaluate immune cell infiltration, with results indicating that samples with higher IFI30 expression had higher infiltration of immune cells, including regulatory T cells and M0 macrophages. Correlation analysis showed that IFI30 was significantly positively correlated with immune checkpoints that suppress effective antitumour immune responses. Immunohistochemical staining was also performed to confirm the association between IFI30 expression and the immune phenotype. The suggested correlation between high IFI30 expression and an immunosuppressive phenotype contributes to our knowledge about the glioma microenvironment and might provide clues for the development of novel therapeutic targets.
| S-EPMC7686962 | biostudies-literature
Project description:BackgroundNeuroblastoma (NB), which is the most frequent and fatal solid tumor in early childhood, lacks an accurate approach to prevent or forecast its recurrence. Dormant NB cells are responsible for metastasis, drug resistance, and suppressive activity in the immune system. However, there is a lack of systematic research on the interaction between dormancy and NB prognosis and its potential associations with tumor immunity.MethodsWe downloaded NB gene expression data and clinical information from the Gene Expression Omnibus and ArrayExpres databases. Based on consensus clustering of the expression of dormancy-associated genes, the NB samples were classified into different groups, and differentially expressed genes (DEGs) were explored in each group. Functional analyses of DEGs were performed, followed by the establishment of a predictive dormancy signature and the assessment of tumor immunity. Finally, sex, age, International Neuroblastoma Staging System (INSS) stage, and MYCN status were identified as independent overall survival-related variables, which were incorporated into the nomogram.ResultsA dormancy-associated gene signature, including CDKN2A, BHLHB3, CDKN2B, MAPK14, CDKN1B, and BMP7, was established. The gene signature showed a strong correlation with NB immune infiltration and capacity to predict NB patient prognosis. A nomogram including MYCN status, INSS stage, age and gene signature risk score was established which further divided NB into high, medium and low-risk groups. This nomogram had certain guiding significance in decision-making for clinical treatment.ConclusionsOur results suggested that the 6-gene genetic signature for NB based on dormancy could predict NB survival and response to immunotherapy.
| S-EPMC10080482 | biostudies-literature
Project description:ObjectiveTo explore the expression of fibronectin type Ⅲ domain containing 1(FNDC1) protein in lung adenocarcinoma and its prognostic significance.MethodsThe expression of FNDC1 in lung adenocarcinoma was predicted by analysis of data from GEO database and GEPIA, and the results were verified by immunohistochemical staining in 92 pairs of clinical specimens of lung adenocarcinoma and adjacent tissues.We further analyzed the correlation of FNDC1 expression with the clinicopathological features of the patients, and evaluated its prognostic value using Cox survival analysis.ResultsAnalysis of the data form GEO database and GEPIA showed a significantly higher expression level of FNDC1 in lung adenocarcinoma than in matched normal tissues (P < 0.05).Kaplan-Meier survival analysis suggested that a high expression of FNDC1 protein was associated with a significantly shorter overall survival time of the patients (P < 0.05).Immunohistochemistry of the clinical specimens also showed a significantly higher protein expression of FNDC1 in lung adenocarcinoma tissues than in paired adjacent tissues (P < 0.001).A high expression of FNDC1 protein was significantly correlated with advanced clinical stage, T stage and N stage (P < 0.05).Cox univariate and multivariate regression survival analysis indicated that an increased expression of FNDC1 was an independent risk factor for poor prognosis of the patients with lung adenocarcinoma (P < 0.05).ConclusionFNDC1 protein is highly expressed in patients with lung adenocarcinoma and in closely related with the occurrence, progression and prognosis of the tumor, suggesting the value of FNDC1 protein as a potential biomarker for assessment of the survival and prognosis of patients with lung adenocarcinoma.
| S-EPMC9458525 | biostudies-literature
Project description:BACKGROUND Gliomas are the most common primary tumors of the brain and spinal cord. The tumor microenvironment (TME) is the cellular environment in which tumors exist. This study aimed to identify the role of the TME and the effects of genes involved in the TME of malignant glioma. MATERIAL AND METHODS The ESTIMATE algorithms in the R package were used to calculate the immune and stromal scores of samples in the TCGA and GSE4290 datasets. The associations of stromal and immune scores with clinicopathological characteristics and overall survival of malignant glioma patients were assessed by analysis of variance and Kaplan-Meier analysis. Differentially expressed genes (DEGs) were obtained through the median immune and stromal score using the R package "limma". Functional enrichment analysis and the PPI network MCODE were used to analyze DEGs. RESULTS Increased immune and stromal scores were closely related with advanced glioma grade and poor prognosis (all P<0.01). In total, 558 DEGs were found and most were related to tumor prognosis. Functional enrichment analysis showed that DEGs were associated with cell-matrix regulation and immune response. Four hub modules related to tumor angiogenesis, collagen formation, and immune response were found and analyzed. Previously overlooked microenvironment-related genes such as LAMB1, FN1, ACTN1, TRIM, SERPINH1, CYBA, LAIR1, and LILRB2 showed prognostic values in malignant glioma patients. CONCLUSIONS The glioma stromal/immune scores are closely related to glioma grade, histology, and survival time. Some glioma microenvironment-related genes including LAMB1, FN1, ACTN1, TRIM6, SERPINH1, CYBA, LAIR1, and LILRB2 show prognostic values in malignant gliomas and serve as potential biomarkers.
| S-EPMC7780890 | biostudies-literature