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通过生物信息学分析识别肝细胞癌中CCL18信号通路内的枢纽基因

Jinlei Mao¹, Yuhang Tao¹, Keke Wang¹

¹State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu, China.

Frontiers in oncology

|March 21, 2024

概括

这项研究显示,CCL18和六个特定的基因 (BMI1,CCR3,CDC25C,CFL1,LDHA,RAC1) 促进肝细胞癌 (HCC) 的进展和免疫规避. 它们的高表达表明预后不佳,并且可以作为HCC中免疫逃避的生物标志物.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
分子生物学分子生物学

背景情况:

肝细胞癌 (HCC) 是癌症相关死亡的主要原因.
CCL18,M2巨细胞激活的标志物,与瘤免疫抑制有关,但其在HCC中的作用尚不清楚.
了解CCL18信号通路对于开发新型HCC治疗策略至关重要.

研究的目的:

调查CCL18及其相关信号通路在HCC的预后意义.
阐明CCL18及其下游基因在HCC进展中的生物功能.
为了确定潜在的生物标志物用于免疫逃避在HCC.

主要方法:

利用TCGA,ICGC和GEO数据库中的RNA-seq数据来识别预后基因.
采用单变量和多变量考克斯回归,以及LASSO回归用于生存分析.
进行了体外实验 (CCK8,EDU,RT-qPCR,西斑,Transwell测试) 来评估细胞功能.
分析了免疫细胞的透,并探索了潜在的治疗点.

主要成果:

在CCL18通路中确定了六个与生存相关的基因 (BMI1,CCR3,CDC25C,CFL1,LDHA,RAC1).
为预测HCC患者生存概率开发了一个名图.
证明了外源性CCL18和六个基因的过度表达促进了HCC细胞的增殖,迁移,入侵,干细胞和PD-L1表达.
在高危HCC患者中观察到免疫抑制和与免疫相关基因的相关性.

结论:

外源性CCL18增强了HCC细胞的增殖,迁移,入侵,干性和免疫逃避.
BMI1,CCR3,CDC25C,CFL1,LDHA和RAC1的高表达是HCC免疫逃避的潜在生物标志物.
准CCL18通路可能为HCC提供一种新的治疗方法.

关键词:

CCL18 CCL18 CCL18 CCL18 CCL18 CCL18 CCL18 CCL18 CCL18 诊断诊断诊断诊断诊断诊断肝细胞癌是肝细胞癌.预后预测预测的预测.瘤微环境是一个微环境.

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