Dataset Information

Expression and prognostic characteristics of m⁵ C regulators in low-grade glioma.

ABSTRACT: Glioma is the most common intracranial malignant tumour. A clear diagnosis and molecular targeted therapy are of great significance for improving the survival time and quality of life of patients with low-grade glioma. 5-methylcytosine methylation is one of the ways of RNA modification, but there are limited studies on the role of m⁵ C methylation of low-grade glioma. Single-nucleotide variant, RNA expression matrix and corresponding clinical data of low-grade glioma came from public database. The single-nucleotide variant and expression of m⁵ C regulators were estimated. A prognostic model based on m⁵ C regulators was constructed by Cox regression. Potential functions of these molecules were assessed by gene set enrichment analysis. DNMT3A mutation was the most frequent among the m⁵ C regulators in low-grade glioma. NSUN3, TET2, TRDMT1, ALYREF, DNMT3B, DNMT1, NOP2 and NSUN2 were up-regulated. One prognostic model was constructed which had a strong predictive power for the overall survival of low-grade glioma. We studied the expression and prognostic characteristics of m⁵ C regulators in low-grade glioma, supplied biomarkers for the diagnosis and prognosis and provided the foundation for the study of the pathogenesis of low-grade glioma.

SUBMITTER: Li X

PROVIDER: S-EPMC7875931 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Expression and prognostic characteristics of m<sup>5</sup> C regulators in low-grade glioma.

Li Xiaozhi X Meng Yutong Y

Journal of cellular and molecular medicine 20210105 3

Glioma is the most common intracranial malignant tumour. A clear diagnosis and molecular targeted therapy are of great significance for improving the survival time and quality of life of patients with low-grade glioma. 5-methylcytosine methylation is one of the ways of RNA modification, but there are limited studies on the role of m<sup>5</sup> C methylation of low-grade glioma. Single-nucleotide variant, RNA expression matrix and corresponding clinical data of low-grade glioma came from public ...[more]

PMID: 33400376

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Project description:PurposeN6-methyladenosine (m6A) is the most prevalent modification in mRNA methylation which has a wide effect on biological functions. This study aims to figure out the efficacy of m6A RNA methylation regulator-based biomarkers with prognostic significance in breast cancer.Patients and methodsThe 23 RNA methylation regulators were firstly analyzed through ONCOMINE, then relative RNA-seq transcriptome and clinical data of 1,096 breast cancer samples and 112 normal tissue samples were acquired from The Cancer Gene Atlas (TCGA) database. The expressive distinction was also showed by the Gene Expression Omnibus (GEO) database. The gene expression data of m6A RNA regulators in human tissues were acquired from the Genotype-Tissue Expression (GTEx) database. The R v3.5.1 and other online tools such as STRING, bc-GeneExminer v4.5, Kaplan-Meier Plotter were applied for bioinformatics analysis.ResultsResults from ONCOMINE, TCGA, and GEO databases showed distinctive expression and clinical correlations of m6A RNA methylation regulators in breast cancer patients. The high expression of YTHDF3, ZC3H13, LRPPRC, and METTL16 indicated poor survival rate in patients with breast cancer, while high expression of RBM15B pointed to a better survival rate. Both univariate and multivariate Cox regression analyses revealed that age and risk scores were related to overall survival (OS). Univariate analysis also delineated that stage, tumor (T) status, lymph node (N) status, and metastasis (M) status were associated with OS. From another perspective, Kaplan-Meier Plotter platform showed that the relatively high expression of YTHDF3 and LRPPRC and the relatively low expression of RBM15B, ZC3H13, and METTL16 in breast cancer patients had worse Relapse-Free Survival (RFS). Breast Cancer Gene-Expression Miner v4.5 showed that LRPPRC level was negatively associated with ER and PR expression, while METTL16, RBM15B, ZC3H13 level was positively linked with ER and PR expression. In HER-2 (+) breast cancer patients, the expression of LRPPRC, METTL16, RBM15B, and ZC3H13 were all lower than the HER-2 (-) group.ConclusionThe significant difference in expression levels and prognostic value of m6A RNA methylation regulators were analyzed and validated in this study. This signature revealed the potential therapeutic value of m6A RNA methylation regulators in breast cancer.

Project description:Purpose: Our current understanding of low-grade brainstem glioma (LGBSG) is still limited. This study aimed to conduct a large-scale population-based real-world study to understand the epidemiological characteristics of LGBSG and determine the predictive factors of cancer-specific survival (CSS) and overall survival (OS) of LGBSG patients. Patients and Methods: We used Surveillance Epidemiology and End Results database to conduct this study of patients with histologically confirmed LGBSG. Patient demographics, tumor characteristics, and treatment options were compared between pediatric and adult patients. Univariate and multivariate analyses were employed to determine prognostic factors of CSS and OS. Kaplan-Meier curve and decision tree were used to confirm the prognostic factors. All variables were further identified by L1-penalized (Lasso) regression and then a nomogram was established to predict the 5- and 8-year CSS and OS rate. The precision of the nomogram was evaluated by calibration plots, Harrell's concordance index, and time-dependent receiver operating characteristic curve. The clinical use of nomogram was estimated by decision curve analysis. Results: A cohort of 305 patients with LGBSG, including 165 pediatric and 140 adult patients, was analyzed. Adult and pediatric patients showed different patterns concerning tumor size, tumor extension, adjuvant therapy, and survival rate. Univariate analysis revealed that pediatric group, gross total resection (GTR), World Health Organization grade II, radiotherapy, extension to ventricular system, and diffuse astrocytic and oligodendroglial tumor (DAOT) were significantly associated with CSS. Multivariate analysis showed that pediatric group, metastasis, ventricular system involvement, and DAOT were independently associated with CSS. The prognostic factors were further confirmed by Kaplan-Meier curve and decision tree. Kaplan-Meier curve also showed that adjuvant therapy added no benefits in patients with GTR and non-GTR. In addition, the nomogram was developed and the C-index of internal validation for CSS was 0.87 (95% CI, 0.78-0.96). Conclusion: This study shows that pediatric and adult patients have different tumor characteristics, treatment options, and survival rate. Pediatric group, DAOT, ventricular system involvement, and metastasis were identified as independent prognostic factors for CSS by multivariate analysis. Adjuvant therapy showed no benefits on CSS in patients with GTR and non-GTR. The nomogram was discriminative and clinically useful.

Project description:BackgroundLow-grade glioma (LGG) is a heterogeneous tumor that might develop into high-grade malignant glioma, which markedly reduces patient survival time. Endocytosis is a cellular process responsible for the internalization of cell surface proteins or external materials into the cytosol. Dysregulated endocytic pathways have been linked to all steps of oncogenesis, from initial transformation to late invasion and metastasis. However, endocytosis-related gene (ERG) signatures have not been used to study the correlations between endocytosis and prognosis in cancer. Therefore, it is essential to develop a prognostic model for LGG based on the expression profiles of ERGs.MethodsThe Cancer Genome Atlas and the Genotype-Tissue Expression database were used to identify differentially expressed ERGs in LGG patients. Gene ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene set enrichment analysis methodologies were adopted for functional analysis. A protein-protein interaction (PPI) network was constructed and hub genes were identified based on the Search Tool for the Retrieval of Interacting Proteins database. Univariate and multivariate Cox regression analyses were used to develop an ERG signature to predict the overall survival (OS) of LGG patients. Finally, the association between the ERG signature and gene mutation status was further analyzed.ResultsSixty-two ERGs showed distinct mRNA expression patterns between normal brain tissues and LGG tissues. Functional analysis indicated that these ERGs were strikingly enriched in endosomal trafficking pathways. The PPI network indicated that EGFR was the most central protein. We then built a 29-gene signature, dividing patients into high-risk and low-risk groups with significantly different OS times. The prognostic performance of the 29-gene signature was validated in another LGG cohort. Additionally, we found that the mutation scores calculated based on the TTN, PIK3CA, NF1, and IDH1 mutation status were significantly correlated with the endocytosis-related prognostic signature. Finally, a clinical nomogram with a concordance index of 0.881 predicted the survival probability of LGG patients by integrating clinicopathologic features and ERG signatures.ConclusionOur ERG-based prediction models could serve as an independent prognostic tool to accurately predict the outcomes of LGG.

Project description:Background: Secreted modular calcium-binding protein 1 (SMOC1) belongs to a family of matricellular proteins; it was involved in embryo development, endothelial cell proliferation, angiogenesis, integrin-matrix interactions, cell adhesion, and regulation of glucose metabolism. Previous studies showed that the expression of SMOC1 was increased in some tumors. However, the prognostic value and the biological function of SMOC1 in tumor remain unclear. Methods: In this study, we explored the expression profile and prognostic value of SMOC1 in pan-cancers, especially glioma, via multiple databases, including Oncomine, Gene Expression Profiling Interactive 2, PrognoScan, Kaplan-Meier plotter, and the Chinese Glioma Genome Atlas database. Furthermore, LinkedOmics was used to identify the genes coexpressed with SMOC1 and to perform Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology analysis in low-grade glioma (LGG). Also, the Cancer Single-Cell State Atlas database was used to evaluate the correlation between SMOC1 expression and functional state activities in glioma cells. In addition, the Tumor Immune Estimation Resource and TISIDB databases were used to evaluate the correlations between SMOC1 expression and tumor-infiltrating immune cells in the tumor microenvironment. Results: Compared with normal brain tissues, the expression of SMOC1 was increased in LGG tissues. The higher expression of SMOC1 was significantly correlated with better survival of LGG patients. Additionally, functional analyses showed that the SMOC1 coexpressed genes were inhibited in processes such as response to type I interferon and interferon-gamma, lymphocyte-mediated immunity, leukocyte migration, adaptive immune response, neutrophil-mediated immunity, T cell activation, and pathways including EMC-receptor interaction, Th17 cell differentiation, and leukocyte trans-endothelial migration in LGG. Moreover, the expression of SMOC1 was correlated with stemness, hypoxia, EMT, and metastasis of glioma cells. Additionally, the expression of SMOC1 expression was negatively correlated with levels of infiltrating B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells, and gene markers of most immune cells in LGG. Conclusion: Our results suggest that SMOC1 could be a potential biomarker to determine prognosis and might play a specific role in the tumor microenvironment of glioma, thereby influencing the development and progression of glioma. These findings provide some new insights for further investigation.

Dataset Information

Expression and prognostic characteristics of m5 C regulators in low-grade glioma.

Publications

Expression and prognostic characteristics of m<sup>5</sup> C regulators in low-grade glioma.

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Expression and prognostic characteristics of m⁵ C regulators in low-grade glioma.