Genetic Determinants of Immune Cells and Hepatocellular Carcinoma Risk: A Bioinformatics and Bidirectional Mendelian Randomization Study
10.3971/j.issn.1000-8578.2025.24.0562
- VernacularTitle: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和双向孟德尔随机化的研究
- Author:
Tong WU
1
;
Fei GAO
2
;
Fei TENG
2
;
Qiaoli ZHANG
3
Author Information
1. Center for Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China.
2. The Third Affiliated Clinical College of Beijing University of Chinese Medicine (The Third Affiliated Hospital), Beijing 100029, China.
3. Department of Minimally Invasive Acupuncture Oncology, The Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing 100029, China.
- Publication Type:BASICRESEARCH
- Keywords:
Mendelian randomization;
Hepatocellular carcinoma;
Immune cell;
Immunophenotype;
SNPs
- From:
Cancer Research on Prevention and Treatment
2025;52(1):42-51
- CountryChina
- Language:Chinese
-
Abstract:
Objective To identify core targets of hepatocellular carcinoma (HCC) by using bioinformatics and specific algorithms, explore their relationships with immune cells, and 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=1.097, 95%CI: 1.002–1.201, P=0.045, PBonferroni=0.091) and CD8 on CD28+ CD45RA+ CD8+ T cell (OR=1.123, 95%CI: 1.027–1.228, P=0.011, PBonferroni=0.022) were the risk factors for HCC. Conversely, HLA DR++ monocyte absolute count was identified as a protective factor for HCC (OR=0.812, 95%CI: 0.702–0.938, P=0.005, PBonferroni=0.139). Conclusion The occurrence and development of liver cancer may be related to CDK1, CCNB1, and CDC20, showing a high degree of correlation with Th2 cells, T helper cells, Th17 cells, and DCs. Mendelian randomization shows that HLA DR on CD33+HLA DR+ CD14dim and CD8 on CD28+CD45RA+CD8+T cells are associated with an increased risk of HCC. The risk of hepatocellular carcinoma is associated with a decrease in the level of HLA DR++monocyte absolute count.
