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

WU Tong; GAO Fei; TENG Fei; ZHANG Qiaoli

doi:10.3971/j.issn.1000-8578.2025.24.0562

Cancer Research on Prevention and Treatment > 2025 > 52(1): 42-51. > DOI: 10.3971/j.issn.1000-8578.2025.24.0562

WU Tong, GAO Fei, TENG Fei, ZHANG Qiaoli. Genetic Determinants of Immune Cells and Hepatocellular Carcinoma Risk: A Bioinformatics and Bidirectional Mendelian Randomization Study[J]. Cancer Research on Prevention and Treatment, 2025, 52(1): 42-51. DOI: 10.3971/j.issn.1000-8578.2025.24.0562

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

WU Tong^1, ,,
GAO Fei^2,,
TENG Fei²,
ZHANG Qiaoli^3, , ,

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

Funding: Beijing Natural Science Foundation General Program (No. 7202122); The Jiebangguashuai Fund Project of the Beijing University of Chinese Medicine (No. 2023-JYB-JBZD-038)

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Corresponding author:
ZHANG Qiaoli, E-mail: zhangqiaoli1009@126.com
Received Date: June 16, 2024
Revised Date: August 25, 2024
Accepted Date: October 20, 2024
Available Online: November 03, 2024

Graphical Abstract

Abstract

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, P_Bonferroni=0.091) and CD8 on CD28⁺ CD45RA⁺ CD8⁺ T cell (OR=1.123, 95%CI: 1.027–1.228, P=0.011, P_Bonferroni=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, P_Bonferroni=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.
- Mendelian randomization,
- Hepatocellular carcinoma,
- Immune cell,
- Immunophenotype,
- SNPs

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Competing interests: The authors declare that they have no competing interests.

References (35)

References

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