在胶质母细胞瘤和低级别胶质瘤中,抗血管生成治疗的反应与AIMP蛋白家族表达有关。

IF 3.3 Q3 ONCOLOGY
Humaira Noor, Yuanning Zheng, Haruka Itakura, Olivier Gevaert
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引用次数: 0

摘要

胶质母细胞瘤(GBM)是一种高度血管化、异质性的肿瘤,然而抗血管生成疗法对生存的益处有限。缺乏有效的预测治疗反应分层的生物标志物仍然是一个主要挑战。氨基酰基tRNA合成酶复合体相互作用多复合体蛋白(AIMPs) 1/2/3与中枢神经系统疾病有关,但其在胶质瘤中的作用尚不清楚。我们研究了它们与血管生成的关系,以及它们作为抗血管生成治疗反应的预测性生物标志物的意义。在这项多队列回顾性研究中,我们分析了来自TCGA、CGGA、Rembrandt、Gravendeel、BELOB和REGOMA试验的胶质瘤样本,以及四个单细胞转录组学数据集。多组学分析包括转录组学、表观遗传学和蛋白质组学数据。Kaplan-Meier和Cox比例风险模型用于评估异质性和均质治疗组AIMPs的潜在预后价值。利用单细胞转录组学,我们探索了AIMP2在GBM中的空间和细胞类型特异性表达。AIMP1/2/3的表达与TCGA肿瘤血管生成显著相关。在胶质瘤中,AIMPs在肿瘤组织与正常组织、高级别胶质瘤组织与低级别胶质瘤组织、复发性肿瘤组织与原发肿瘤组织中均上调
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Response to Antiangiogenic Therapy Is Associated with AIMP Protein Family Expression in Glioblastoma and Lower-Grade Gliomas.

Glioblastoma (GBM) is a highly vascularized, heterogeneous tumor, yet antiangiogenic therapies have yielded limited survival benefits. The lack of validated predictive biomarkers for treatment response stratification remains a major challenge. Aminoacyl tRNA synthetase complex-interacting multicomplex proteins (AIMP) 1/2/3 have been implicated in central nervous system diseases, but their roles in gliomas remain unexplored. We investigated their association with angiogenesis and their significance as predictive biomarkers for antiangiogenic treatment response. In this multi-cohort retrospective study, we analyzed glioma samples from The Cancer Genome Atlas, Chinese Glioma Genome Atlas, REMBRANDT, Gravendeel, BELOB, and REGOMA trials, and four single-cell transcriptomic datasets. Multiomic analyses incorporated transcriptomic, epigenetic, and proteomic data. Kaplan-Meier and Cox proportional hazards models were used to assess the potential prognostic value of AIMPs in heterogeneous and homogeneous treatment groups. Using single-cell transcriptomics, we explored spatial and cell type-specific AIMP2 expression in GBM. AIMP1/2/3 expressions correlated significantly with angiogenesis across The Cancer Genome Atlas cancers. In gliomas, AIMPs were upregulated in tumor versus normal tissues, higher- versus lower-grade gliomas, and recurrent versus primary tumors (P < 0.05). Upon retrospective analysis of two clinical trials assessing different antiangiogenic drugs, we found that high-AIMP2 subgroups had improved response to therapies in GBM [REGOMA: HR, 4.75 (1.96-11.5), P < 0.001; BELOB: HR, 2.3 (1.17-4.49), P = 0.015]. AIMP2-cg04317940methylation emerged as a clinically applicable stratification marker. Single-cell analysis revealed homogeneous AIMP2 expression in tumor tissues, particularly in astrocyte-like cells, suggesting a mechanistic link to tumor angiogenesis. These findings provide novel insights into the role of AIMPs in angiogenesis, offering improved patient stratification and therapeutic outcomes in recurrent GBM.

Significance: This study identifies AIMP2 as a novel biomarker predictive of antiangiogenic treatment response in recurrent GBM. Through multiomic and single-cell analyses, AIMP2 is shown to be upregulated in aggressive gliomas and linked to angiogenesis. Its expression and methylation status offer a clinically applicable stratification tool, enabling more personalized therapeutic approaches and improved outcomes in patients receiving antiangiogenic therapies.

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