识别与临床特征相关的替代拼接:从胰腺癌到泌尿生殖系统瘤
Chen Duan1, Yangjun Zhang2,3, Lu Li4
1Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Frontiers in oncology
|October 9, 2023
概括
替代拼接事件 (ASE) 显著影响癌症,影响瘤异质性. 这项研究将特定的ASEs与临床特征联系起来,并确定了尿路癌症进展中的关键调节者,如TUBB3和PCBP2.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 分子生物学分子生物学
背景情况:
- 替代拼接事件 (ASE) 促使瘤异质性在生殖尿路和其他癌症.
- 在各种癌症中ASE的临床相关性仍然不完全理解.
研究的目的:
- 在33种不同的瘤类型中全面描述ASEs的临床病理相关性.
- 研究ASEs,免疫细胞透和临床特征之间的关联.
- 探索ASEs的调控机制,包括SNP影响和RNA结合蛋白.
主要方法:
- 对 TCGA SpliceSeq 和 UCSC Xena 数据库对 ASE 和临床数据的分析.
- 使用CIBERSORT和TIMER2.0进行免疫细胞透分析.
- 综合拼接定量特征位点 (sQTLs) 数据和RNA结合蛋白质基因丰富分析.
主要成果:
- 在24种癌症类型中确定了30种临床特征,每个癌症类型与50多种ASEs相关.
- 在免疫细胞透中发现了与初级诊断和疾病类型相关的显著差异.
- 在脏清细胞癌 (KIRC) 中发现了与SNP相关的ASE,并在转移中确定了GIT2和TUBB3替代拼接.
- 定点RNA结合蛋白 (PCBP2,SNRNP70,HuR) 可能会调节膀泌尿腺癌 (BLCA) 的拼接.
结论:
- ASEs在多种癌症类型中具有显著的临床相关性.
- 替代拼接TUBB3和像PCBP2这样的RNA结合蛋白被证实是泌尿器官癌症进展的关键调节剂.
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