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转录组和蛋白质组范围的关联研究确定了与细胞癌相关的基因

Diptavo Dutta¹, Xinyu Guo², Timothy D Winter³

¹Integrative Tumor Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.

American journal of human genetics

|August 13, 2024

概括

这项研究使用先进的关联研究确定了细胞癌 (RCC) 的新型遗传点. 这些发现优先考虑了分子候选人,用于进一步实验室研究癌的发展和风险因素.

科学领域:

遗传学遗传学是一个
在瘤学瘤学.
生物信息学是一种生物信息学.

背景情况:

细胞癌 (RCC) 是一个重要的健康问题,具有复杂的遗传基础.
确定分子点对于开发RCC有效的诊断和治疗策略至关重要.

研究的目的:

在细胞癌 (RCC) 实验室研究中提名和优先考虑分子标.
利用整合性基因组和转录基因组分析来加强RCC易感基因的发现.

主要方法:

对RCC进行了全转录组关联研究 (TWAS) 和全蛋白组关联研究 (PWAS).
利用来自大型队列 (29,020例,835670例对照) 的全基因组关联研究 (GWAS) 数据.
在多个脏和瘤转录组 (GTEx,TCGA-KIRC,TCGA-KIRP) 和48个GTEx组织中综合TWAS发现.

主要成果:

在四个脏转录组中的至少两个中确定了38个显著的基因关联 (FDR <5%),其中12个独立于GWAS位置.
通过结合48个组织的TWAS数据,在瘤转录组中发现了23个额外的可复制关联.
揭示了清细胞RCC和乳头RCC的亚型特定基因关联,两者都有三个共同点.
PWAS确定了13种相关的蛋白质,映射到GWAS的位置.
在RCC细胞中,TWAS基因在活性调节区域和缺氧诱导因子结合部位中被丰富.

结论:

该研究成功地提名并优先考虑了RCC易感性的潜在分子标.
综合性TWAS和PWAS提供了一个强大的框架,用于识别RCC的新型遗传贡献者.
确定了RCC和常见癌症/危险因素之间的共同遗传贡献,表明了潜在的共同途径.

关键词:

在HIF中,我们可以看到HIF.它们包括TWAS/PWAS.促进者/增强者细胞癌瘤是细胞癌.小型类型亚型类型敏感性基因是敏感性的基因.

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