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BMC Cancer
Published in: BMC Cancer 1/2023

Open Access 01-12-2023 | Glioblastoma | Research

CRISPR-Cas9 identifies growth-related subtypes of glioblastoma with therapeutical significance through cell line knockdown

Authors: Nannan Zhao, Siyuan Weng, Zaoqu Liu, Hui Xu, Yuqin Ren, Chunguang Guo, Long Liu, Zhenyu Zhang, Yuchen Ji, Xinwei Han

Published in: BMC Cancer | Issue 1/2023

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Abstract

Background

Glioblastoma (GBM) is a type of highly malignant brain tumor that is known for its significant intratumoral heterogeneity, meaning that there can be a high degree of variability within the tumor tissue. Despite the identification of several subtypes of GBM in recent years, there remains to explore a classification based on genes related to proliferation and growth.

Methods

The growth-related genes of GBM were identified by CRISPR-Cas9 and univariate Cox regression analysis. The expression of these genes in the Cancer Genome Atlas cohort (TCGA) was used to construct growth-related genes subtypes (GGSs) via consensus clustering. Validation of this subtyping was performed using the nearest template prediction (NTP) algorithm in two independent Gene Expression Omnibus (GEO) cohorts and the ZZ cohort. Additionally, copy number variations, biological functions, and potential drugs were analyzed for each of the different subtypes separately.

Results

Our research established multicenter-validated GGSs. GGS1 exhibits the poorest prognosis, with the highest frequency of chr 7 gain & chr 10 loss, and the lowest frequency of chr 19 & 20 co-gain. Additionally, GGS1 displays the highest expression of EGFR. Furthermore, it is significantly enriched in metabolic, stemness, proliferation, and signaling pathways. Besides we showed that Foretinib may be a potential therapeutic agent for GGS1, the worst prognostic subtype, through data screening and in vitro experiments. GGS2 has a moderate prognosis, with a slightly higher proportion of chr 7 gain & chr 10 loss, and the highest proportion of chr 19 & 20 co-gain. The prognosis of GGS3 is the best, with the least chr 7 gain & 10 loss and EGFR expression.

Conclusions

These results enhance our understanding of the heterogeneity of GBM and offer insights for stratified management and precise treatment of GBM patients.
Appendix
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Metadata
Title
CRISPR-Cas9 identifies growth-related subtypes of glioblastoma with therapeutical significance through cell line knockdown
Authors
Nannan Zhao
Siyuan Weng
Zaoqu Liu
Hui Xu
Yuqin Ren
Chunguang Guo
Long Liu
Zhenyu Zhang
Yuchen Ji
Xinwei Han
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-11131-7

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