单细胞多基因组学揭示了B2M介导的骨髓细胞重编程,并构建了早期肝细胞癌复发的预测模型
Zhenyao Tan1,2, Yezhen Tang3, Bendong Chen1,2
1Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, Yinchuan, China.
早期肝细胞癌 (HCC) 复发是一个挑战. 这项研究使用多组学来发现与B2M相关的免疫变化导致复发,提供了一个预测工具和潜在的治疗方法.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 基因组学就是基因组学.
背景情况:
- 肝细胞癌 (HCC) 早期复发是一个重大的临床挑战.
- 推动早期HCC复发的潜在分子机制仍然不完全理解.
研究的目的:
- 通过使用综合性多组学方法,研究早期HCC复发 (在2年内复发) 的分子驱动因素.
- 为早期HCC复发开发一个预测框架.
主要方法:
- 单细胞RNA测序,蛋白质组学,转录组学和临床数据的整合.
- 识别与复发相关的蛋白质和途径.
- 单细胞免疫分析和功能分析.
- 使用LASSO回归的预测模型的开发和验证.
主要成果:
- 确定了14种与复发相关的蛋白质 (例如CD274,B2M,MYC,CASP3).
- 转录基因分析显示MYC-TARGETS-V2和INTERFERON-GAMMA-RESPONSE通路的丰富性.
- 单细胞分析显示,在复发性瘤中,免疫透率降低,骨髓状细胞 (cDC2,巨细胞) 表现出B2M相关的重编程 (HLA下调,改变了GAS6/PROS1信号).
- 一个基于cDC2和巨细胞特征的预测模型显示了中等的性能 (AUC>0.65).
结论:
- 在复发性HCC中,B2M可能在重塑免疫微环境方面发挥作用.
- 这项研究提供了对早期HCC复发机制的见解.
- 综合性单细胞多组学方法提供了一个具有潜在治疗意义的初步预测工具,包括针对B2M相关途径使用诸如vandetanib之类的药物.
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