恶性胶质母细胞瘤（GBM）是一种高度恶性的脑肿瘤，其显著的肿瘤内异质性意味着在肿瘤组织中可能存在较高程度的变异性。尽管近年来已经鉴定出几个GBM亚型，但仍需探索基于增殖和生长相关基因的分类。通过CRISPR-Cas9和单变量Cox回归分析鉴定了GBM的生长相关基因。利用癌症基因组图谱（TCGA）队列中这些基因的表达数据，通过一致性聚类构建了生长相关基因亚型（GGSs）。该亚型的验证通过两个独立的基因表达组学数据库（GEO）队列和ZZ队列中的最近模板预测（NTP）算法进行。另外，给定不同亚型分别分析了拷贝数变异、生物功能和潜在药物。我们的研究建立了多中心验证的GGSs。GGS1具有最差的预后，最高的chr 7增益与chr 10缺失频率，最低的chr 19和20共增益频率。此外，GGS1的EGFR表达最高，同时在代谢、干细胞、增殖和信号通路中显著富集。此外，我们通过数据筛选和体外实验发现，Foretinib可能是GGS1的潜在治疗药物，GGS1是最糟糕的预后亚型。GGS2的预后适中，chr 7增益与chr 10缺失的比例稍高，chr 19和20共增益的比例最高。GGS3的预后最佳，chr 7增益与10缺失最少，EGFR表达最低。这些结果增进了我们对GBM异质性的理解，并为GBM患者的分层管理和精确治疗提供了启示。© 2023 BioMed Central Ltd.，Springer Nature的一部分。

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.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.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.These results enhance our understanding of the heterogeneity of GBM and offer insights for stratified management and precise treatment of GBM patients.© 2023. BioMed Central Ltd., part of Springer Nature.