免疫细胞与肝细胞癌风险的遗传决定因素：一项基于生物信息学及双向孟德尔随机化的研究

吴桐; 高菲; 滕飞; 张巧丽

doi:10.3971/j.issn.1000-8578.2025.24.0562

免疫细胞与肝细胞癌风险的遗传决定因素：一项基于生物信息学及双向孟德尔随机化的研究

Genetic Determinants of Immune Cells and Hepatocellular Carcinoma Risk: A Bioinformatics and Bidirectional Mendelian Randomization Study

摘要

摘要: 　　目的：基于生物信息学及特定算法筛选肝细胞癌的核心靶点并探讨其与免疫细胞的关系，并通过孟德尔随机化探讨免疫细胞与肝细胞癌的因果关系。方法：通过GEO和TCGA数据库对肝细胞癌发生的相关基因进行筛选，并通过GSVA和CIBERSORT算法进行免疫浸润分析，随后对免疫细胞与肝细胞癌的因果关系进行双向孟德尔随机化分析。结果：筛选出284个肝癌相关基因，在蛋白互作网络中获取到120个相关基因，免疫浸润分析显示关键基因与免疫细胞之间具有较好的相关性。孟德尔随机化结果显示：HLA DR on CD33⁺ HLA DR⁺ CD14dim（OR=1.0971, 95%CI: 1.0019～1.2013, P= 0.0453，P_Bonferroni =0.0906）和CD8 on CD28⁺ CD45RA⁺ CD8⁺ T cell(OR= 1.1227, 95%CI: 1.0267～1.2276, P= 0.0112，P_Bonferroni = 0.0224)是肝细胞癌的危险因素；肝细胞癌是HLA DR⁺⁺ monocyte Absolute Count（OR= 0.8119, 95%CI: 0.7024～0.9383, P= 0.0048，P_Bonferroni = 0.1385）的保护因素。结论：本研究基于生物信息学并结合孟德尔随机化，从遗传角度首次全面的揭示了肝细胞癌的发病机制及与免疫细胞之间的关系，为未来个体化治疗提供指导。

Abstract: Objective: This study aims to identify core targets in hepatocellular carcinoma (HCC) using bioinformatics and specific algorithms, to explore their relationships with immune cells, and to investigate the causal relationships between immune cells and HCC through Mendelian randomization.
Methods: Relevant genes associated with the development of HCC were screened using the GEO and TCGA databases. Immune infiltration analysis was conducted using GSVA and CIBERSORT algorithms. A bidirectional Mendelian randomization analysis was then performed to explore the causal relationships between immune cells and HCC.
Results: A total of 284 HCC-related genes were identified, with 120 genes recognized within the protein interaction network. Immune infiltration analysis revealed significant correlations between key genes and immune cells. Mendelian randomization results indicated that HLA DR on CD33+ HLA DR+ CD14dim (OR=1.0971, 95%CI:1.0019–1.2013, P=0.0453, P_Bonferroni=0.0906) and CD8 on CD28+ CD45RA+ CD8+ T cell (OR=1.1227, 95%CI: 1.0267–1.2276, P=0.0112, P_Bonferroni=0.0224) are risk factors for HCC. Conversely, HLA DR++ monocyte Absolute Count was identified as a protective factor for HCC (OR=0.8119, 95%CI: 0.7024–0.9383, P=0.0048, P_Bonferroni=0.1385).
Conclusion: This study, integrating bioinformatics with Mendelian randomization, comprehensively reveals the genetic mechanisms of HCC development and its relationship with immune cells from a genetic perspective for the first time. These findings provide guidance for future personalized treatment strategies for HCC.

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