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多Omics分析确定了阿尔德海德脱酶2作为Treg介导免疫抑制微环境和肝细胞癌之间的交叉交流中的关键调解者
Zhi-Yong Liu1,2, Xia-Hui Lin1,2, Hong-Ying Guo1,2
1Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200030, China.
International journal of biological sciences
|May 10, 2024
概括
这项研究表明,阿尔代脱酶 (ALDH) 基因失调会影响肝癌 (HCC) 的进展. 一种特定的ALDH基因特征识别了具有抑制免疫细胞的高风险HCC患者,提供了新的治疗点.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 生物化学 生物化学
背景情况:
- 化脱酶 (ALDH) 家族基因失调与包括癌症在内的各种疾病有关.
- 目前还没有对ALDH变化的全面分析及其在肝细胞癌 (HCC) 中的治疗意义.
研究的目的:
- 系统地评估ALDH基因表达和HCC的功能性改变.
- 为了确定基于ALDH的生物标志物用于HCC预后和治疗向.
- 阐明ALDH失调,免疫抑制和HCC发病之间的机制联系.
主要方法:
- 对HCC组织和正常肝脏组织进行多组分析 (转录组学,单细胞分析).
- 开发和验证用于预后预测的四基因ALDH签名.
- 研究ALDH2的功能,酸化及其在调节T调控细胞 (Treg) 分化和信号通路中的作用.
主要成果:
- 在19个ALDH基因中,有15个被发现在HCC中被转录失调.
- 一个四个基因的签名 (ALDH2,ALDH5A1,ALDH6A1,ALDH8A1) 准确地预测了HCC的预后,并确定了增加Treg透的高危子组.
- 瘤坏死因子受体超级家族成员18 (TNFRSF18) 在高危HCC中选择性地过度表达Tregs.
- ALDH2被确定为HCC中的瘤抑制剂,具有新的酸化位增强其活性.
- ALDH2通过抑制HCC中的β-catenin/TGF-β1信号通路来抑制Treg分化.
结论:
- 一个集成的ALDH-Tregs-TNFRSF18轴有助于HCC的发病.
- 鉴定到的ALDH基因特征可以作为HCC的强有力的预后生物标志物.
- 准ALDH-Tregs-TNFRSF18轴为HCC提供了一个潜在的治疗策略.
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