整合全基因组关联研究和转录组学,确定脑膜瘤药物靶点的优先次序。

IF 4.1 Q1 CLINICAL NEUROLOGY
Brain communications Pub Date : 2025-02-05 eCollection Date: 2025-01-01 DOI:10.1093/braincomms/fcaf053
Wan-Zhe Liao, Jia-He Wang, Hua-Jie Zhong, Shen-Yu Wen, Yang Chen, Jia-Qi Chen, Xue-Kun Zhang, Xin-Yi Wu, Jia-Nuo Tan, Kun-Yi Li, Shao-Cong Mo, Li-Jun Wang
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引用次数: 0

摘要

脑膜瘤是一种常见的中枢神经系统肿瘤,在神经肿瘤学领域提出了重大挑战。本研究利用全基因组关联研究(GWAS)和转录组学分析来阐明脑膜瘤的病理基础,并率先发现新的药物靶点。通过基于汇总数据的孟德尔随机化(SMR)、共定位分析和孟德尔随机化,我们确定了四个基因作为关键的治疗靶点。整体和单细胞RNA测序的整合证实了脑膜瘤组织中三个基因(XBP1, TTC28和TRPC6)的表达上调,揭示了它们的细胞分布,并暗示了肿瘤内在的异质性。分子对接进一步确定了地塞米松和左炔诺孕酮作为这些靶点的潜在调节剂,为个性化脑膜瘤治疗策略铺平了道路。这项研究促进了我们对脑膜瘤分子景观的理解,并说明了基因组和转录组整合在精确肿瘤学领域的力量。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Integrating genome-wide association studies and transcriptomics prioritizes drug targets for meningioma.

Meningioma, a prevalent central nervous system tumour, presents a significant challenge in neuro-oncology. This study harnesses genome-wide association studies (GWAS) and transcriptomic analysis to illuminate the pathological underpinnings of meningioma and spearhead the discovery of novel drug targets. By employing summary-data-based Mendelian randomization (SMR), colocalization analyses and Mendelian randomization, we pinpointed four genes as pivotal therapeutic targets. The integration of bulk and single-cell RNA sequencing confirmed the upregulated expression of three of the genes (XBP1, TTC28 and TRPC6) in meningioma tissues, unravelling their cellular distribution and hinting at the tumour's intrinsic heterogeneity. Molecular docking further identified dexamethasone and levonorgestrel as potential modulators of these targets, paving the way for personalized meningioma treatment strategies. This research advances our understanding of meningioma's molecular landscape and illustrates the power of genomic and transcriptomic integration in the realm of precision oncology.

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CiteScore
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