肝细胞癌微环境的变化在不同未折叠的蛋白质反应活性状态中的变化
Yao Wang1, Xiao Fei Zhu1, Wan Jian Gu1
1Department of Clinical Laboratory, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, No. 155, Han'Zhong Road, Qinhuai, Nanjing, 210029, Jiangsu, China.
Discover oncology
|March 26, 2025
概括
在肝细胞癌 (HCC) 中,高解折蛋白响应 (UPR) 活性与支持性较低的瘤微环境和较差的患者预后相关. 特定的基因下调,包括CLEC3B,RAMP3,GPR182和DNASE1L3,与这些负面结果有关.
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:
- 展开的蛋白质反应 (UPR) 是一个关键的细胞途径,参与应激适应.
- UPR在抗癌药物耐药性和瘤微环境 (TME) 调节方面发挥着重要作用.
- 了解UPR对肝细胞癌 (HCC) TME的影响对于治疗开发至关重要.
研究的目的:
- 为了研究高UPR活性HCC的瘤微环境 (TME) 的变化.
- 为了确定关键的调节基因与UPR驱动的TME变化相关的HCC.
- 为了将UPR活动,TME特征和HCC患者预后相关联.
主要方法:
- 基于HCC的UPR活性进行差异性基因表达分析.
- 分析差异表达基因的信号通路和生物功能.
- 使用TCGA数据 (xCell,ESTIMATE) 计算免疫/流体得分和透细胞丰度.
- 与UPR相关的基因与微环境得分和细胞群的相关性分析 (R包"corrplot").
主要成果:
- 与UPR相关的基因主要参与与免疫相关的信号通路.
- 具有高UPR活性的HCC组织表现出明显较低的Stromal得分和减少各种透细胞 (例如HSC,LEC,EC,脂肪细胞) 的丰度.
- 降低的 stromal 评分和透的 stromal 细胞与更糟糕的 HCC 预后相关.
- CLEC3B,RAMP3,GPR182和DNASE1L3的下调与较低的Stromal得分,透细胞减少和HCC预后较差有关.
结论:
- 具有高UPR活性的HCC的特点是瘤微环境不太有利 (较低的Stromal得分) 和患者预后更差.
- 在高UPR条件下,下调基因CLEC3B,RAMP3,GPR182和DNASE1L3可能是修改HCC微环境的关键调节者.
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