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Peer-reviewedCC BY-NC-ND 4.0ILIVER

LILRB4 expression is associated with macrophage enrichment and differential survival in hepatocellular carcinoma

4 affiliations
  1. 1Senior Department of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital, Beijing 100853, China
  2. 2Chinese People's Liberation Army Medical School, Beijing 100853, China
  3. 3Graduate School, Kunming Medical University, Kunming 650500, China
  4. 4Graduate School, Chongqing Medical University, Chongqing 400010, China

Abstract

Background and aims: The clinical and immune-cell context of leukocyte immunoglobulin-like receptor B4 (LILRB4) in hepatocellular carcinoma (HCC) remains incompletely characterized. This study aimed to characterize LILRB4 expression across cell types and examine its associations with survival outcomes and macrophage-related immune features in HCC.

Methods: Public liver hepatocellular carcinoma (LIHC) resources were analyzed using survival, transcriptomic, functional enrichment, immune deconvolution, and single-cell analyses. Survival analyses included 373 patients for overall survival and 365 for disease-specific survival. Kaplan–Meier analyses compared two expression groups (high and low), defined using outcome-selected cutpoints obtained from maximally selected rank statistics. Continuous-expression Cox models provided complementary analyses.

Results: Higher LILRB4 expression was associated with shorter overall survival (OS) in an outcome-selected analysis (n = 373; low-expression group, 250; high-expression group, 123; Cox hazard ratio [HR], 1.524; 95% confidence interval [CI], 1.074–2.162; log-rank p = 0.017). Continuous LILRB4 expression was associated with OS in univariable and adjusted Cox models (adjusted HR, 1.246; 95% CI, 1.010–1.537), whereas continuous expression was not significantly associated with disease-specific survival (HR, 1.137; 95% CI, 0.916–1.412). LILRB4 expression correlated with macrophage enrichment (Spearman rs = 0.755) and M2-like macrophage estimates from quanTIseq (rs = 0.544) and CIBERSORT-ABS (rs = 0.753). Single-cell resources localized LILRB4 mainly to monocyte/macrophage populations.

Conclusion: LILRB4 expression is associated with macrophage-enriched immune features and adverse survival patterns in LIHC. These findings identify LILRB4 as a candidate marker of the macrophage-rich HCC microenvironment that warrants further investigation of its prognostic and immunoregulatory relevance.

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BibTeX
@article{liu2026lilrb4,
  title = {{LILRB4 expression is associated with macrophage enrichment and differential survival in hepatocellular carcinoma}},
  author = {Qi Liu and Yuyang Liu and Junyi Chen and Tao Wan and Chao Li and Ning Zhang and Zhanyu Yang},
  journal = {ILIVER},
  year = {2026},
  month = oct,
  doi = {10.1016/j.iliver.2026.100278},
  url = {https://doi.org/10.1016/j.iliver.2026.100278},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - LILRB4 expression is associated with macrophage enrichment and differential survival in hepatocellular carcinoma
AU  - Qi Liu
AU  - Yuyang Liu
AU  - Junyi Chen
AU  - Tao Wan
AU  - Chao Li
AU  - Ning Zhang
AU  - Zhanyu Yang
PY  - 2026
DA  - 2026/10/12
JO  - ILIVER
DO  - 10.1016/j.iliver.2026.100278
UR  - https://doi.org/10.1016/j.iliver.2026.100278
AB  - Background and aims: The clinical and immune-cell context of leukocyte immunoglobulin-like receptor B4 (LILRB4) in hepatocellular carcinoma (HCC) remains incompletely characterized. This study aimed to characterize LILRB4 expression across cell types and examine its associations with survival outcomes and macrophage-related immune features in HCC.  Methods: Public liver hepatocellular carcinoma (LIHC) resources were analyzed using survival, transcriptomic, functional enrichment, immune deconvolution, and single-cell analyses. Survival analyses included 373 patients for overall survival and 365 for disease-specific survival. Kaplan–Meier analyses compared two expression groups (high and low), defined using outcome-selected cutpoints obtained from maximally selected rank statistics. Continuous-expression Cox models provided complementary analyses.  Results: Higher LILRB4 expression was associated with shorter overall survival (OS) in an outcome-selected analysis (n = 373; low-expression group, 250; high-expression group, 123; Cox hazard ratio [HR], 1.524; 95% confidence interval [CI], 1.074–2.162; log-rank p = 0.017). Continuous LILRB4 expression was associated with OS in univariable and adjusted Cox models (adjusted HR, 1.246; 95% CI, 1.010–1.537), whereas continuous expression was not significantly associated with disease-specific survival (HR, 1.137; 95% CI, 0.916–1.412). LILRB4 expression correlated with macrophage enrichment (Spearman rs = 0.755) and M2-like macrophage estimates from quanTIseq (rs = 0.544) and CIBERSORT-ABS (rs = 0.753). Single-cell resources localized LILRB4 mainly to monocyte/macrophage populations.  Conclusion: LILRB4 expression is associated with macrophage-enriched immune features and adverse survival patterns in LIHC. These findings identify LILRB4 as a candidate marker of the macrophage-rich HCC microenvironment that warrants further investigation of its prognostic and immunoregulatory relevance.
SN  - 2772-9478
ER  -