Mendelian randomization analysis of immune cell populations, serum metabolites and hepatocellular carcinoma risk
Abstract Background Hepatocellular carcinoma (HCC) remains highly lethal globally, with complex pathogenic mechanisms. This study employs Mendelian randomization (MR) to investigate causal relationships between immune cells, serum metabolites, and HCC risk. Methods A two-sample Mendelian randomizati...
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Springer
2025-07-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-03037-6 |
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| author | Wei Shen Yuanying Zeng |
| author_facet | Wei Shen Yuanying Zeng |
| author_sort | Wei Shen |
| collection | DOAJ |
| description | Abstract Background Hepatocellular carcinoma (HCC) remains highly lethal globally, with complex pathogenic mechanisms. This study employs Mendelian randomization (MR) to investigate causal relationships between immune cells, serum metabolites, and HCC risk. Methods A two-sample Mendelian randomization (2SMR) design was employed, based on large-scale genome-wide association studies (GWAS) databases, selecting single nucleotide polymorphisms (SNPs) strongly associated with immune cell features and plasma metabolites as genetic instrumental variables. The inverse variance weighted (IVW). method was primarily used for effect size estimation, with robustness verified through multiple sensitivity analysis methods including MR-Egger regression and weighted median method. Results MR analysis revealed three immune cell subpopulations causally associated with HCC: CD127 on CD28 + CD4 + T cells (OR = 1.31, 95% CI: 1.15–1.49), unswitched memory B cell percentage (OR = 1.57, 95% CI: 1.23–2.01). Four causal serum metabolites were identified: 5-hydroxylysine (OR = 0.64), isobutyrylcarnitine (OR = 1.67), 1-stearoyl-GPC (OR = 0.27), and glycosyl-N-tricosanoyl-sphingadienine (OR = 0.32). For plasma metabolites, four metabolites were significantly associated with HCC risk: 5-hydroxylysine (OR = 0.64), isobutyrylcarnitine (OR = 1.67), 1-stearoyl-GPC (OR = 0.27), and glycosyl-N-tricosanoyl-sphingadienine (OR = 0.32). Conclusion This multi-omics approach provides evidence for causal relationships between specific immune populations, metabolites, and HCC risk, identifying potential biomarkers and therapeutic targets for HCC prevention and treatment. |
| format | Article |
| id | doaj-art-250467a5be584a3a8673d14c3ef58ccd |
| institution | Kabale University |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-250467a5be584a3a8673d14c3ef58ccd2025-08-20T04:01:35ZengSpringerDiscover Oncology2730-60112025-07-0116111410.1007/s12672-025-03037-6Mendelian randomization analysis of immune cell populations, serum metabolites and hepatocellular carcinoma riskWei Shen0Yuanying Zeng1Oncology Department, The Affiliated Suzhou Hospital of Nanjing Medical UniversityOncology Department, The Affiliated Suzhou Hospital of Nanjing Medical UniversityAbstract Background Hepatocellular carcinoma (HCC) remains highly lethal globally, with complex pathogenic mechanisms. This study employs Mendelian randomization (MR) to investigate causal relationships between immune cells, serum metabolites, and HCC risk. Methods A two-sample Mendelian randomization (2SMR) design was employed, based on large-scale genome-wide association studies (GWAS) databases, selecting single nucleotide polymorphisms (SNPs) strongly associated with immune cell features and plasma metabolites as genetic instrumental variables. The inverse variance weighted (IVW). method was primarily used for effect size estimation, with robustness verified through multiple sensitivity analysis methods including MR-Egger regression and weighted median method. Results MR analysis revealed three immune cell subpopulations causally associated with HCC: CD127 on CD28 + CD4 + T cells (OR = 1.31, 95% CI: 1.15–1.49), unswitched memory B cell percentage (OR = 1.57, 95% CI: 1.23–2.01). Four causal serum metabolites were identified: 5-hydroxylysine (OR = 0.64), isobutyrylcarnitine (OR = 1.67), 1-stearoyl-GPC (OR = 0.27), and glycosyl-N-tricosanoyl-sphingadienine (OR = 0.32). For plasma metabolites, four metabolites were significantly associated with HCC risk: 5-hydroxylysine (OR = 0.64), isobutyrylcarnitine (OR = 1.67), 1-stearoyl-GPC (OR = 0.27), and glycosyl-N-tricosanoyl-sphingadienine (OR = 0.32). Conclusion This multi-omics approach provides evidence for causal relationships between specific immune populations, metabolites, and HCC risk, identifying potential biomarkers and therapeutic targets for HCC prevention and treatment.https://doi.org/10.1007/s12672-025-03037-6Mendelian randomizationHepatocellular carcinomaImmune cellsMetabolitesTumor microenvironment |
| spellingShingle | Wei Shen Yuanying Zeng Mendelian randomization analysis of immune cell populations, serum metabolites and hepatocellular carcinoma risk Discover Oncology Mendelian randomization Hepatocellular carcinoma Immune cells Metabolites Tumor microenvironment |
| title | Mendelian randomization analysis of immune cell populations, serum metabolites and hepatocellular carcinoma risk |
| title_full | Mendelian randomization analysis of immune cell populations, serum metabolites and hepatocellular carcinoma risk |
| title_fullStr | Mendelian randomization analysis of immune cell populations, serum metabolites and hepatocellular carcinoma risk |
| title_full_unstemmed | Mendelian randomization analysis of immune cell populations, serum metabolites and hepatocellular carcinoma risk |
| title_short | Mendelian randomization analysis of immune cell populations, serum metabolites and hepatocellular carcinoma risk |
| title_sort | mendelian randomization analysis of immune cell populations serum metabolites and hepatocellular carcinoma risk |
| topic | Mendelian randomization Hepatocellular carcinoma Immune cells Metabolites Tumor microenvironment |
| url | https://doi.org/10.1007/s12672-025-03037-6 |
| work_keys_str_mv | AT weishen mendelianrandomizationanalysisofimmunecellpopulationsserummetabolitesandhepatocellularcarcinomarisk AT yuanyingzeng mendelianrandomizationanalysisofimmunecellpopulationsserummetabolitesandhepatocellularcarcinomarisk |