Exploring the potential biomarkers for prognosis of glioblastoma via weighted gene co-expression network analysis

Mengyuan Zhang; Zhike Zhou; Zhouyang Liu; Fangxi Liu; Chuansheng Zhao

doi:10.7717/peerj.12768

Exploring the potential biomarkers for prognosis of glioblastoma via weighted gene co-expression network analysis

PeerJ. 2022 Jan 18:10:e12768. doi: 10.7717/peerj.12768. eCollection 2022.

Authors

Mengyuan Zhang¹, Zhike Zhou², Zhouyang Liu¹, Fangxi Liu¹, Chuansheng Zhao¹

Affiliations

¹ Department of Neurology and Stroke Center, The First Hospital of China Medical University, Shenyang, China.
² Department of Geriatrics, The First Hospital of China Medical University, Shenyang, China.

Abstract

Background: Glioblastoma (GBM) is the most common malignant tumor in the central system with a poor prognosis. Due to the complexity of its molecular mechanism, the recurrence rate and mortality rate of GBM patients are still high. Therefore, there is an urgent need to screen GBM biomarkers to prove the therapeutic effect and improve the prognosis.

Results: We extracted data from GBM patients from the Gene Expression Integration Database (GEO), analyzed differentially expressed genes in GEO and identified key modules by weighted gene co-expression network analysis (WGCNA). GSE145128 data was obtained from the GEO database, and the darkturquoise module was determined to be the most relevant to the GBM prognosis by WGCNA (r = - 0.62, p = 0.01). We performed enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to reveal the interaction activity in the selected modules. Then Kaplan-Meier survival curve analysis was used to extract genes closely related to GBM prognosis. We used Kaplan-Meier survival curves to analyze the 139 genes in the darkturquoise module, identified four genes (DARS/GDI2/P4HA2/TRUB1) associated with prognostic GBM. Low expression of DARS/GDI2/TRUB1 and high expression of P4HA2 had a poor prognosis. Finally, we used tumor genome map (TCGA) data, verified the characteristics of hub genes through Co-expression analysis, Drug sensitivity analysis, TIMER database analysis and GSVA analysis. We downloaded the data of GBM from the TCGA database, the results of co-expression analysis showed that DARS/GDI2/P4HA2/TRUB1 could regulate the development of GBM by affecting genes such as CDC73/CDC123/B4GALT1/CUL2. Drug sensitivity analysis showed that genes are involved in many classic Cancer-related pathways including TSC/mTOR, RAS/MAPK.TIMER database analysis showed DARS expression is positively correlated with tumor purity (cor = 0.125, p = 1.07e-02)), P4HA2 expression is negatively correlated with tumor purity (cor =-0.279, p = 6.06e-09). Finally, GSVA analysis found that DARS/GDI2/P4HA2/TRUB1 gene sets are closely related to the occurrence of cancer.

Conclusion: We used two public databases to identify four valuable biomarkers for GBM prognosis, namely DARS/GDI2/P4HA2/TRUB1, which have potential clinical application value and can be used as prognostic markers for GBM.

Keywords: Biomarkers; GEO; Glioblastoma; Prognosis; Weighted gene co-expression network analysis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers, Tumor / genetics
Brain Neoplasms* / diagnosis
Gene Regulatory Networks / genetics
Glioblastoma* / genetics
Humans
Prognosis

Substances

Biomarkers, Tumor

Grants and funding

This study was supported by the Program for Liaoning Innovative Research Team in University (NO.LT2019015) and the LiaoNing Revitalization Talents Program and Liaoning Key R&D Guidance Program (NO. 2019JH8/10300002). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.