{"title":"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。","authors":"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","doi":"10.1093/braincomms/fcaf053","DOIUrl":null,"url":null,"abstract":"<p><p>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 (<i>XBP1</i>, <i>TTC28</i> and <i>TRPC6</i>) 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.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf053"},"PeriodicalIF":4.1000,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880806/pdf/","citationCount":"0","resultStr":"{\"title\":\"Integrating genome-wide association studies and transcriptomics prioritizes drug targets for meningioma.\",\"authors\":\"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\",\"doi\":\"10.1093/braincomms/fcaf053\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 (<i>XBP1</i>, <i>TTC28</i> and <i>TRPC6</i>) 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.</p>\",\"PeriodicalId\":93915,\"journal\":{\"name\":\"Brain communications\",\"volume\":\"7 2\",\"pages\":\"fcaf053\"},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2025-02-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880806/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Brain communications\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1093/braincomms/fcaf053\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Brain communications","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/braincomms/fcaf053","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
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.