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膀癌变体具有共同的攻击性特征,包括CA125+细胞状态和可向的TM4SF1表达
Heiko Yang1,2, Hanbing Song3, Elizabeth Yip3
1Department of Urology, University of California San Francisco, San Francisco, CA, USA.
Nature communications
|June 17, 2025
概括
组织学变异性膀癌表现出侵略性特征和对治疗的抵抗性. 向TM4SF1显示出治疗这些具有挑战性的尿路细胞癌亚型的希望.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 分子病理学分子病理学
背景情况:
- 膀癌的基因组变异 (HV) 亚型相比传统泌尿腺癌 (UC) 具有攻击性和耐治疗性.
- 高密度膀癌独特生物学的分子和转录基础在很大程度上仍未被描述.
研究的目的:
- 为了确定独特的转录程序驱动攻击性表型的组织学变异性膀癌.
- 在这些确定的计划中探索潜在的治疗点.
主要方法:
- 单细胞RNA测序用于分析组织学变异中的瘤细胞状态.
- 表达分析侧重于特定的基因,包括MUC16,MUC4,KRT24和TM4SF1.1.
- 化学抗原受体 (CAR) T细胞疗法在体外和体内对TM4SF1进行了评估.
主要成果:
- 在HVs中发现了一种独特的瘤细胞状态,其特征是MUC16,MUC4和KRT24表达.
- 这种细胞状态与转移潜力,预测的化疗耐药性和患者生存率低下有关.
- 在HV瘤细胞中观察到TM4SF1的增强表达.
- 针对TM4SF1的CAR T细胞显示出特定的抗癌活性.
结论:
- 膀癌的组织学变体具有独特的细胞状态,与预后不佳和治疗耐药性有关.
- TM4SF1代表了一种有前途的治疗点,用于治疗侵袭性组织学变异性膀癌.
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