识别与编程细胞死亡相关的亚型揭示了结肠癌中的免疫异质性和治疗分歧
Peng Xia1,2, Ying Qu2,3, Quanzhong Liu2,3
1School of Biological Science & Medical Engineering, Southeast University, Nanjing 211189, China.
Theranostics
|March 9, 2026
概括
我们根据编程细胞死亡 (PCD) 途径确定了三种结肠腺癌亚型. 一个亚型 (PCDS3) 显示对治疗的耐药性,并且可能从针对MDK-SDC2轴的sunitinib中受益.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 治疗耐药性是结肠腺癌 (COAD) 的一个主要挑战.
- 编程细胞死亡 (PCD) 途径的失调影响治疗反应和瘤微环境 (TME).
- 在COAD的TME和临床异质性中PCD的综合作用尚不清楚.
研究的目的:
- 根据PCD路径对COAD亚型进行分类.
- 分析这些亚型的基因组,TME和治疗特征.
- 为了确定抗性COAD的潜在治疗策略.
主要方法:
- 从1,140名COAD患者的综合转录组数据使用非负矩阵因子化 (NMF) 来建立与编程细胞死亡相关的亚型 (PCDS) 分类.
- 在独立队列中验证的亚型.
- 使用多omics数据,计算药物重新定位,分子对接和in silico药物敏感性分析来表征亚型.
主要成果:
- 确定了三个强大的PCDS亚型:PCDS1 (免疫激活),PCDS2 (WNT/TP53信号传递) 和PCDS3 (介质细胞,T细胞功能障碍/排除).
- 富含iCAFs的PCDS3显示出不良的预后和对化疗和免疫治疗的耐药性.
- 在PCDS3中发现MDK-SDC2轴激活,与T细胞功能障碍相关,并确定sunitinib作为潜在的针对PCDS3的药物.
结论:
- 根据PCD失调,TME重塑和治疗结果,确定了COAD的新型分子亚型.
- MDK-SDC2轴与PCDS3.3中的 stromal介导免疫疗法耐药性有关.
- 用sunitinib准MDK-SDC2轴可能会克服致命的PCDS3瘤中的抗性.
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