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在BCG治疗后膀癌进展中的TGF-β信号传递和瘤微环境动态:一个纵向单核RNA-seq研究

Seo-Young Lee^1,2, Yun-Hee Lee³, Tae-Min Kim^4,5,6

¹Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

|November 11, 2025

概括

这项研究通过分析瘤微环境动态,揭示了BCG治疗后非肌肉侵入性膀癌 (NMIBC) 的进展情况. 确定了关键的途径和细胞相互作用,为改善NMIBC治疗提供了洞察力.

科学领域:

泌尿器科泌尿器科泌尿器科泌尿器科
在瘤学瘤学.
基因组学就是基因组学.

背景情况:

无肌肉侵入性膀癌 (NMIBC) 经常复发和进展,尽管有巴塞勒斯卡尔梅特-盖林 (BCG) 治疗.
驱动BCG耐药性和NMIBC进展的细胞机制尚不清楚.
了解瘤微环境 (TME) 对于开发有效的NMIBC治疗至关重要.

研究的目的:

研究NMIBC的TME中的转录动态和细胞相互作用.
确定与BCG耐药性和疾病进展相关的关键途径和细胞亚型.

主要方法:

在9例NMIBC病例中进行了纵向单核RNA测序 (snRNA-seq).
分析包括58,037个细胞核的细胞类型/亚型注释和细胞与细胞相互作用分析.
样本包括治疗前和疾病进展后的状态.

主要成果:

在恶性细胞中观察到显著的患者间异质性,与进展相关的拷贝数变化.
从治疗前到进展后,TGF-β信号逐渐得到丰富.
不同的TME亚型,包括LAMP3+树突细胞和iCAF纤维细胞,显示出与进展相关的轨迹.
像DSC2-DSG2和ENG-BMPR2这样的灵受体对与糟糕的结果有关.

结论:

这项研究阐明了BCG治疗后膀癌进展的细胞和分子机制.
snRNA-seq确定了关键的TME亚型,TGF-β信号传递和体受体相互作用 (DSC2-DSG2,ENG-BMPR2) 作为潜在的生物标志物.
结果为增强治疗策略和改善NMIBC患者结果提供了见解.

关键词:

在BCG中,BCG是BCG.膀癌是一种癌症.纤维母细胞细胞是如何形成的巨细胞是一个巨细胞.单细胞测序是一种单细胞测序.在TGF-β信号传输中.

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