细胞内膜网膜应激通过调节免疫力促进肝细胞癌:基于人工神经网络和单细胞测序的研究
Zhaorui Cheng1, Shuangmei Li1, Shujun Yang1
1Department of Emergency, The Eighth Affiliated Hospital of Sun Yat- sen University, Shenzhen, 518003, Guangdong, P. R. China.
Journal of translational medicine
|July 15, 2024
概括
这项研究开发了一种可靠的人工神经网络模型,通过分析内质网膜压力相关基因 (ERSRGs) 来诊断肝细胞癌 (HCC). 该模型对早期诊断和在HCC中识别新的治疗点充满希望.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 生物信息学是一种生物信息学.
背景情况:
- 肝细胞癌 (HCC) 呈现出复杂的发病机制,有限的治疗方法和不良预后.
- 细胞内膜网膜应激 (ERS) 与HCC的发展有关,需要对分子机制进行进一步的研究,以改善诊断和治疗.
- 识别HCC的新型诊断和治疗点至关重要.
研究的目的:
- 开发基于内分泌网膜压力相关基因 (ERSRGs) 的HCC诊断的预测模型.
- 研究ERSRG与瘤免疫微环境之间的相关性.
- 为了确定潜在的治疗药物和关键基因用于HCC治疗.
主要方法:
- 集成多个基因表达总 (GEO) 数据集以识别ERSRG.
- 应用机器学习技术 (随机森林,支持矢量机器,人工神经网络) 用于模型构建和基因选.
- 利用ESTIMATE算法进行免疫微环境分析和药物签名数据库 (DSigDB) 进行药物发现.
- 进行单细胞测序,细胞通信分析和体外功能实验,以验证中央基因PPP1R16A.
主要成果:
- 使用六个具有高曲线下面面积 (AUC) 值的ERSRG (SRPX,THBS4,CTH,PPP1R16A,CLGN,THBS1) 来构建一个准确的人工神经网络 (ANN) 模型来诊断HCC.
- ERSRG的表达水平与免疫细胞透和与免疫相关的途径有显著的相关性,这表明免疫治疗的潜力.
- 确定PPP1R16A是一种具有高突变率的核心基因,可能通过MIF/CD74+/CXCR4通路影响瘤微环境;其敲击抑制了HCC细胞的增殖,迁移和入侵.
- 莫梅塔松被预测为一个有前途的治疗药物.
结论:
- 通过使用机器学习和人工智能,建立了用于ERS相关的HCC诊断的新型预测模型.
- 这项研究为诊断和治疗HCC提供了新的见解和方向.
- 这些发现突显了ERSRG作为HCC中的生物标志物和治疗点的潜力.
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