Dataset Information

Comprehensive analysis of the clinical and biological significances of cholesterol metabolism in lower-grade gliomas.

ABSTRACT:

Background

As a component of membrane lipids and the precursor of oxysterols and steroid hormones, reprogrammed cholesterol metabolism contributes to the initiation and progression of multiple cancers. Thus, we aim to further investigate the significances of cholesterol metabolism in lower-grade gliomas (LGGs).

Methods

The present study included 413 LGG samples from TCGA RNA-seq dataset (training cohort) and 172 LGG samples from CGGA RNA-seq dataset (validation cohort). The cholesterol metabolism-related signature was identified by the LASSO regression model. Bioinformatics analyses were performed to explore the functional roles of this signature in LGGs. Kaplan-Meier and Cox regression analyses were enrolled to estimate prognostic value of the risk signature.

Results

Our findings suggested that cholesterol metabolism was tightly associated clinicopathologic features and genomic alterations of LGGs. Bioinformatics analyses revealed that cholesterol metabolism played a key role in immunosuppression of LGGs, mainly by promoting macrophages polarization and T cell exhaustion. Kaplan-Meier curve and Cox regression analysis showed that cholesterol metabolism was an independent prognostic indicator for LGG patients. To improve the clinical application value of the risk signature, we also constructed a nomogram model to predict the 1-, 3- and 5-year survival of LGG patients.

Conclusion

The cholesterol metabolism was powerful prognostic indicator and could serve as a promising target to enhance personalized treatment of LGGs.

SUBMITTER: Tao R

PROVIDER: S-EPMC10364387 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

Comprehensive analysis of the clinical and biological significances of cholesterol metabolism in lower-grade gliomas.

Tao Rui R Huang Ruoyu R Yang Jingchen J Wang Jiangfei J Wang Kuanyu K

BMC cancer 20230724 1

<h4>Background</h4>As a component of membrane lipids and the precursor of oxysterols and steroid hormones, reprogrammed cholesterol metabolism contributes to the initiation and progression of multiple cancers. Thus, we aim to further investigate the significances of cholesterol metabolism in lower-grade gliomas (LGGs).<h4>Methods</h4>The present study included 413 LGG samples from TCGA RNA-seq dataset (training cohort) and 172 LGG samples from CGGA RNA-seq dataset (validation cohort). The choles ...[more]

PMID: 37488496

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Project description:BackgroundDiffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II and III) have highly variable clinical behavior that is not adequately predicted on the basis of histologic class. Some are indolent; others quickly progress to glioblastoma. The uncertainty is compounded by interobserver variability in histologic diagnosis. Mutations in IDH, TP53, and ATRX and codeletion of chromosome arms 1p and 19q (1p/19q codeletion) have been implicated as clinically relevant markers of lower-grade gliomas.MethodsWe performed genomewide analyses of 293 lower-grade gliomas from adults, incorporating exome sequence, DNA copy number, DNA methylation, messenger RNA expression, microRNA expression, and targeted protein expression. These data were integrated and tested for correlation with clinical outcomes.ResultsUnsupervised clustering of mutations and data from RNA, DNA-copy-number, and DNA-methylation platforms uncovered concordant classification of three robust, nonoverlapping, prognostically significant subtypes of lower-grade glioma that were captured more accurately by IDH, 1p/19q, and TP53 status than by histologic class. Patients who had lower-grade gliomas with an IDH mutation and 1p/19q codeletion had the most favorable clinical outcomes. Their gliomas harbored mutations in CIC, FUBP1, NOTCH1, and the TERT promoter. Nearly all lower-grade gliomas with IDH mutations and no 1p/19q codeletion had mutations in TP53 (94%) and ATRX inactivation (86%). The large majority of lower-grade gliomas without an IDH mutation had genomic aberrations and clinical behavior strikingly similar to those found in primary glioblastoma.ConclusionsThe integration of genomewide data from multiple platforms delineated three molecular classes of lower-grade gliomas that were more concordant with IDH, 1p/19q, and TP53 status than with histologic class. Lower-grade gliomas with an IDH mutation either had 1p/19q codeletion or carried a TP53 mutation. Most lower-grade gliomas without an IDH mutation were molecularly and clinically similar to glioblastoma. (Funded by the National Institutes of Health.).

Project description:BackgroundThe therapeutic effects of conventional treatment on gliomas are not promising. The tumor microenvironment (TME) has a close association with the invasiveness of multiple types of tumors, including low-grade gliomas (LGG). This study aims to validate the prognostic and immune-related role of macrophage scavenger receptor 1 (MSR1) in LGG patients.MethodsData in this study were obtained from public databases. The differential expression of MSR1 was analyzed in LGG patients with different clinicopathological characteristics. Kaplan-Meier survival analysis, a time-dependent receiver operating characteristic (ROC) curve, and Cox regression analysis were used to assess the prognostic value of MSR1. Differentially expressed genes (DEGs) were screened between the high and low expression groups of MSR1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to annotate the function of these DEGs. Hallmark gene sets were identified based on MSR1 by Gene Set Enrichment Analysis (GSEA). Difference analysis and correlation analysis were used to study the relationship between MSR1 and TME-related scores, tumor-infiltrating immune cells (TIICs), immune-related gene sets, and immune checkpoints (ICPs). The single-cell sequencing data were processed to identify the cell types expressing MSR1. The quantification of TIICs in TME was calculated by single-sample gene set enrichment analysis (ssGSEA). The differential expression of MSR1 in LGG and control brain tissues was verified by experiments.ResultsThere were significant differences in the expression level of MSR1 in different types of tissues and cells. MSR1 has a high prognostic value in LGG patients and can be used as an independent prognostic factor. MSR1 is closely related to TME and may play an important role in the immunotherapy of LGG patients.ConclusionsThe result of our study demonstrated that MSR1 is an independent prognostic biomarker in LGG patients and may play an important role in the TME of LGGs.

Dataset Information

Comprehensive analysis of the clinical and biological significances of cholesterol metabolism in lower-grade gliomas.

Background

Methods

Results

Conclusion

Publications

Comprehensive analysis of the clinical and biological significances of cholesterol metabolism in lower-grade gliomas.

Similar Datasets

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