Cargando…

Molecular Features of Glioma Determined and Validated Using Combined TCGA and GTEx Data Analyses

Gliomas are among the most common intracranial tumors which originated from neuroepithelial cells. Increasing evidence has revealed that long noncoding RNA (lncRNA)-microRNA (miRNA)-mRNA module regulation and tumor-infiltrating immune cells play important regulatory roles in the occurrence and progr...

Descripción completa

Detalles Bibliográficos
Autores principales: Yang, Zijiang, Gong, Weiyi, Zhang, Ting, Gao, Heng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516354/
https://www.ncbi.nlm.nih.gov/pubmed/34660294
http://dx.doi.org/10.3389/fonc.2021.729137
_version_ 1784583786447503360
author Yang, Zijiang
Gong, Weiyi
Zhang, Ting
Gao, Heng
author_facet Yang, Zijiang
Gong, Weiyi
Zhang, Ting
Gao, Heng
author_sort Yang, Zijiang
collection PubMed
description Gliomas are among the most common intracranial tumors which originated from neuroepithelial cells. Increasing evidence has revealed that long noncoding RNA (lncRNA)-microRNA (miRNA)-mRNA module regulation and tumor-infiltrating immune cells play important regulatory roles in the occurrence and progression of gliomas. However, the precise underlying molecular mechanisms remain largely unknown. Data on gliomas in The Cancer Genome Atlas lack normal control samples; to overcome this limitation, we combined 665 The Cancer Genome Atlas glioma RNA sequence datasets with 188 Genotype-Tissue Expression normal brain RNA sequences to construct an expression matrix profile after normalization. We systematically analyzed the expression of mRNAs, lncRNAs, and miRNAs between gliomas and normal brain tissues. Kaplan–Meier survival analyses were conducted to screen differentially expressed mRNAs, lncRNAs, and miRNAs. A prognostic miRNA-related competitive endogenous RNA network was constructed, and the core subnetworks were filtered using 6 miRNAs, 3 lncRNAs, and 11 mRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to investigate the biological functions of significantly dysregulated mRNAs. Co-expression network analysis was performed to analyze and screen the core genes. Furthermore, single-sample Gene Set Enrichment Analysis and immune checkpoint gene expression analysis were performed, as co-expression analysis indicated immune gene dysregulation in glioma. Finally, the expression of representative dysregulated genes was validated in U87 cells at the transcriptional level, establishing a foundation for further research. We identified 7017 mRNAs, 437 lncRNAs, and 9 miRNAs that were differentially expressed in gliomas. Kaplan–Meier survival analysis revealed 5684 mRNAs, 61 lncRNAs, and 7 miRNAs with potential as prognostic signatures in patients with glioma. The hub subnetwork of the competing endogenous RNA network between PART1-hsa-mir-25-SLC12A5/TACC2/BSN/TLN2/ZDHHC8 was screened out. Gene co-expression network, single-sample Gene Set Enrichment Analysis, and immune checkpoint expression analysis demonstrated that tumor-infiltrating immune cells are closely related to gliomas. We identified novel potential biomarkers to predict survival and therapeutic targets for patients with gliomas based on a large-scale sample. Importantly, we filtered pivotal genes that provide valuable information for further exploration of the molecular mechanisms underlying glioma tumorigenesis and progression.
format Online
Article
Text
id pubmed-8516354
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-85163542021-10-15 Molecular Features of Glioma Determined and Validated Using Combined TCGA and GTEx Data Analyses Yang, Zijiang Gong, Weiyi Zhang, Ting Gao, Heng Front Oncol Oncology Gliomas are among the most common intracranial tumors which originated from neuroepithelial cells. Increasing evidence has revealed that long noncoding RNA (lncRNA)-microRNA (miRNA)-mRNA module regulation and tumor-infiltrating immune cells play important regulatory roles in the occurrence and progression of gliomas. However, the precise underlying molecular mechanisms remain largely unknown. Data on gliomas in The Cancer Genome Atlas lack normal control samples; to overcome this limitation, we combined 665 The Cancer Genome Atlas glioma RNA sequence datasets with 188 Genotype-Tissue Expression normal brain RNA sequences to construct an expression matrix profile after normalization. We systematically analyzed the expression of mRNAs, lncRNAs, and miRNAs between gliomas and normal brain tissues. Kaplan–Meier survival analyses were conducted to screen differentially expressed mRNAs, lncRNAs, and miRNAs. A prognostic miRNA-related competitive endogenous RNA network was constructed, and the core subnetworks were filtered using 6 miRNAs, 3 lncRNAs, and 11 mRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to investigate the biological functions of significantly dysregulated mRNAs. Co-expression network analysis was performed to analyze and screen the core genes. Furthermore, single-sample Gene Set Enrichment Analysis and immune checkpoint gene expression analysis were performed, as co-expression analysis indicated immune gene dysregulation in glioma. Finally, the expression of representative dysregulated genes was validated in U87 cells at the transcriptional level, establishing a foundation for further research. We identified 7017 mRNAs, 437 lncRNAs, and 9 miRNAs that were differentially expressed in gliomas. Kaplan–Meier survival analysis revealed 5684 mRNAs, 61 lncRNAs, and 7 miRNAs with potential as prognostic signatures in patients with glioma. The hub subnetwork of the competing endogenous RNA network between PART1-hsa-mir-25-SLC12A5/TACC2/BSN/TLN2/ZDHHC8 was screened out. Gene co-expression network, single-sample Gene Set Enrichment Analysis, and immune checkpoint expression analysis demonstrated that tumor-infiltrating immune cells are closely related to gliomas. We identified novel potential biomarkers to predict survival and therapeutic targets for patients with gliomas based on a large-scale sample. Importantly, we filtered pivotal genes that provide valuable information for further exploration of the molecular mechanisms underlying glioma tumorigenesis and progression. Frontiers Media S.A. 2021-09-30 /pmc/articles/PMC8516354/ /pubmed/34660294 http://dx.doi.org/10.3389/fonc.2021.729137 Text en Copyright © 2021 Yang, Gong, Zhang and Gao https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Yang, Zijiang
Gong, Weiyi
Zhang, Ting
Gao, Heng
Molecular Features of Glioma Determined and Validated Using Combined TCGA and GTEx Data Analyses
title Molecular Features of Glioma Determined and Validated Using Combined TCGA and GTEx Data Analyses
title_full Molecular Features of Glioma Determined and Validated Using Combined TCGA and GTEx Data Analyses
title_fullStr Molecular Features of Glioma Determined and Validated Using Combined TCGA and GTEx Data Analyses
title_full_unstemmed Molecular Features of Glioma Determined and Validated Using Combined TCGA and GTEx Data Analyses
title_short Molecular Features of Glioma Determined and Validated Using Combined TCGA and GTEx Data Analyses
title_sort molecular features of glioma determined and validated using combined tcga and gtex data analyses
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516354/
https://www.ncbi.nlm.nih.gov/pubmed/34660294
http://dx.doi.org/10.3389/fonc.2021.729137
work_keys_str_mv AT yangzijiang molecularfeaturesofgliomadeterminedandvalidatedusingcombinedtcgaandgtexdataanalyses
AT gongweiyi molecularfeaturesofgliomadeterminedandvalidatedusingcombinedtcgaandgtexdataanalyses
AT zhangting molecularfeaturesofgliomadeterminedandvalidatedusingcombinedtcgaandgtexdataanalyses
AT gaoheng molecularfeaturesofgliomadeterminedandvalidatedusingcombinedtcgaandgtexdataanalyses