与免疫检查点相关的长非编码RNAs核心调节电路的景观揭示了对免疫调节和免疫治疗反应的含义
Changfan Qu1, Hao Cui2, Song Xiao1
1College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
Communications biology
|March 15, 2024
概括
这项研究确定了长非编码RNAs (lncRNAs) 调节免疫检查点 (ICPs) 以预测免疫治疗反应. 这些与ICP相关的lncRNA三胞胎可以改善癌症预后和免疫检查点抑制剂 (ICI) 的生物标志物发现.
科学领域:
- 癌症免疫学和免疫疗法
- 非编码RNA生物学
- 生物信息学和计算生物学
背景情况:
- 长非编码RNAs (lncRNAs) 越来越多地被认为是它们在调节基因表达中的作用,包括免疫检查点 (ICPs).
- 大多数lncRNAs在瘤免疫中的精确功能以及它们作为预测免疫检查点抑制剂 (ICI) 反应的生物标志物的潜力在很大程度上仍未被探索.
- 准确预测ICI反应对于优化癌症治疗策略至关重要.
研究的目的:
- 开发一个完整的框架来识别调节ICP和免疫基因的lncRNA.
- 发现基于lncRNA的新生物标志物,用于预测患者对免疫检查点抑制剂 (ICI) 的反应.
- 阐明lncRNAs在瘤免疫调节中的作用及其改善癌症预后的潜力.
主要方法:
- 使用基于网络的分析和贝叶斯网络推理,开发一个综合框架.
- 识别与ICP相关的LncRNAs介导的核心调节电路三重组 (ICP-LncCRCTs) 涉及lncRNAs,ICPs和免疫基因.
- 在多个独立数据集中使用机器学习算法预测预后和ICI响应的ICP-LncCRCTs的验证.
主要成果:
- 识别与枢纽ICP相关的lncRNAs (例如,MIR155HG,ADAMTS9-AS2),它们对免疫调节至关重要.
- 证明特定的ICP相关的lncRNA与免疫细胞透,MHC和CYT相关,并且可以区分癌症亚型.
- 与单个分子相比,ICP-LncCRCTs (例如CXCL10-MIR155HG-ICOS) 显示出对黑色素瘤患者预后的优异预测.
- 在多个数据集中,ICP-LncCRCTs有效预测了ICI反应,ICP-LncCRCTs和瘤突变负担 (TMB) 的结合进一步提高了ICI治疗黑色素瘤的预测准确度.
结论:
- 这项研究提供了一个强大的框架,用于识别瘤免疫中的IncRNA介导的调节电路.
- ICP-LncCRCT作为有前途的生物标志物用于预测癌症预后和对免疫检查点抑制剂的反应.
- 这项工作促进了对癌症免疫学中的lncRNA功能的理解,并加速了基于lncRNA的治疗策略的发现.
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