Identification of key genes involved in the recurrence of glioblastoma multiforme using weighted gene co-expression network analysis and differential expression analysis

ABSTRACT

Glioblastoma multiforme (GBM) is the most fatal malignancy, and despite extensive treatment, tumors inevitably recur. This study aimed to identify recurrence-associated molecules in GBM. The gene expression profile GSE139533, containing 70 primary and 47 recurrent GBM tissues and their corresponding clinical traits, was downloaded from the Gene Expression Omnibus (GEO) database and used for weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) analysis. After identifying the hub genes which differentially expressed in recurrent GBM tissues and in the gene modules correlated with recurrence, data from the Chinese Glioma Genome Atlas (CCGA) and The Cancer Genome Atlas (TCGA) databases were analyzed with GSE43378 to determine the relationship between hub genes and patient prognosis. The diagnostic value of the identified hub genes was verified using 52 GBM tissues. Three gene modules were correlated with recurrence and 2623 genes were clustered in these clinically significant modules. Among these, 13 genes – EHF, TRPM1, FXYD4, CDH15, LHX5, TP73, FBN3, TLX1, C1QL4, COL2A, SEC61G, NEUROD4 and GPR139 – were differentially expressed in recurrent GBM samples; low LHX5 and TLX1 expression predicted poor outcomes. LHX5 and TLX1 expression showed weak positive relationships with Karnofsky performance scale scores. Additionally, LHX5 and TLX1 expression was found to be decreased in our recurrent GBM samples compared with that in primary samples; these genes exhibited high diagnostic value in distinguishing recurrent samples from primary samples. Our findings indicate that LHX5 and TLX1 might be involved in GBM recurrence and act as potential biomarkers for this condition.

Graphical abstract

KEYWORDS:

• Glioblastoma multiforme
• wgcna
• deg analysis
• recurrence

Research highlights

1. TLX1 and LHX5 were present in the gene modules associated with recurrence.

2. TLX1 and LHX5 expression was decreased in the recurrent GBM tissues.

3. Low expression levels of TLX1 and LHX5 were associated with poor outcomes.

4. TLX1 and LHX5 have potential to distinguish recurrent from primary GBM tissues.

Acknowledgements

Not applicable.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Consent to participate

All patients signed the informed consent forms, and the Human Research Ethics Review Committee of the Affiliated Hospital of Weifang Medical University approved and administered the use of collected tissues.

Data availability statement

The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request.

GEO database (https://www.ncbi.nlm.nih.gov/gds)

GSEA (https://software.broad institute. org/gsea/index.jsp)

CCGA (http://www.cgga.org.cn/)

TCGA (https://xenabrowser.net/datapages/)

Author contribution

ZhiRui Zeng and HongMei Zhang designed the research, supervised the experiment and contributed to the manuscript revision; Peng Ren and JingYa Wang performed the experiments and wrote the manuscript; Lei Li, XiaoWan Lin, GuangHan Wu and JiaYi Chen analyzed the data. All authors have read and agreed to submit the final version of the manuscript.

Supplementary material

Supplemental data for this article can be accessed here

Additional information

Funding

This work was supported by the Education Department of the Guizhou Province Project under Grant [number YJSCXJH (2020) 147]