空间时空转录学的整合性分析界定了状瘤发育中的动态细胞状态
Varsha Sreekanth1,2, Timur Rusanov1,3, Farah Yousef1,3
1Department of Biochemistry and Molecular Genetics, University of Illinois, College of Medicine, Chicago, IL.
bioRxiv : the preprint server for biology
|November 19, 2025
概括
状细胞癌的存活率很低,原因是免疫治疗的耐药性. 在癌前阶段表皮细胞基因表达的早期变化可能会驱动这种抗性,影响治疗结果.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 基因组学就是基因组学.
背景情况:
- 状细胞癌 (SCCs) 占癌症死亡的20%,生存率落后于腺癌.
- 在SCC,特别是头癌中,免疫疗法的有效性有限,与治疗耐药性有关,影响不到10%的早期患者.
- 在SCC中潜在的内在耐药性的机制尚不清楚,并且可能起源于前性或失塑性状态.
研究的目的:
- 调查口腔状上皮质的转录组变化,跨越扩张不良到癌症连续性.
- 确定驱动早期状细胞癌症治疗耐药性的分子机制.
主要方法:
- 产生一组数据集的小鼠和人类口腔状表皮从前性阶段到侵袭性癌症.
- 单细胞和空间转录组学数据的综合分析.
- 空间知情的细胞与细胞相互作用分析.
主要成果:
- 在表皮转录组中观察到早期和持续的变化,跨越了异位形成症到癌症连续性.
- 在严重的发育不良和侵袭性癌症中,确定了伤口愈合和免疫重塑计划的发育不良特异性上调.
- 这些转录组程序甚至存在于早期的发育不良阶段.
结论:
- 口腔状上皮质的早期转录组变化先于侵袭性癌症.
- 在早期发育不良时,伤口愈合和免疫重塑计划的升级可能会导致SCCs的攻击性.
- 了解这些早期的分子变化对于克服状细胞癌的内在治疗阻力至关重要.
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