HSPA5 and FGFR1 genes in the mesenchymal subtype of glioblastoma can improve a treatment efficacy.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
ACS Applied Bio Materials Pub Date : 2024-05-18 eCollection Date: 2024-01-01 DOI:10.1080/19768354.2024.2347538
Ju Young Lee, Jongkeun Park, Dongwan Hong
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Abstract

Tyrosine kinase inhibitors (TKIs) have emerged as a potential treatment strategy for glioblastoma multiforme (GBM). However, their efficacy is limited by various drug resistance mechanisms. To devise more effective treatments for GBM, genetic characteristics must be considered in addition to pre-existing treatments. We performed an integrative analysis with heterogeneous GBM datasets of genomic, transcriptomic, and proteomic data from DepMap, TCGA and CPTAC. We found that poor prognosis was induced by co-upregulation of heat shock protein family A member 5 (HSPA5) and fibroblast growth factor receptor 1 (FGFR1). Co-up regulation of these two genes could regulate the PI3K/AKT pathway. GBM cell lines with co-upregulation of these two genes showed higher drug sensitivity to PI3K inhibitors. In the mesenchymal subtype, the co-upregulation of FGFR1 and HSPA5 resulted in the most malignant subtype of GBM. Furthermore, we found this newly discovered subtype was correlated with homologous recombination deficiency (HRD) In conclusion, we discovered novel druggable candidates within the group exhibiting co-upregulation of these two genes in GBM, suggest potential strategies for combination therapy.

间质亚型胶质母细胞瘤中的 HSPA5 和 FGFR1 基因可提高治疗效果。
酪氨酸激酶抑制剂(TKIs)已成为多形性胶质母细胞瘤(GBM)的一种潜在治疗策略。然而,它们的疗效受到各种耐药机制的限制。为了设计出更有效的 GBM 治疗方法,除了现有的治疗方法外,还必须考虑遗传特征。我们利用来自 DepMap、TCGA 和 CPTAC 的基因组、转录组和蛋白质组异构 GBM 数据集进行了综合分析。我们发现,热休克蛋白家族 A 成员 5(HSPA5)和成纤维细胞生长因子受体 1(FGFR1)的共调控诱导了不良预后。这两个基因的共调控可调节 PI3K/AKT 通路。这两个基因共同上调的 GBM 细胞系对 PI3K 抑制剂的药物敏感性更高。在间质亚型中,FGFR1 和 HSPA5 的共重复性导致 GBM 亚型的恶性程度最高。此外,我们还发现这种新发现的亚型与同源重组缺陷(HRD)相关。总之,我们发现了GBM中这两个基因共调控群体中的新型药物候选者,并提出了联合治疗的潜在策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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