ArticleScientific reports2025
Construction of a macrophage-related prognostic signature and assessment of immune checkpoint inhibitor efficacy of HCC.
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Immune checkpoint inhibitor-induced cardiotoxicity: from immune mechanisms to clinical surveillance and targeted therapies.Frontiers in cardiovascular medicine · 2026Review
- Identification and validation of prognostic genes related to glycolysis and M2 macrophage in hepatocellular carcinoma: an integrated analysis of bulk RNA sequencing and single-cell RNA sequencing.Frontiers in immunology · 2026Article
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Authors and funding
5 authors.
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Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death, with limited treatment options and high recurrence rates. Prognostic biomarkers and predictors of immune checkpoint inhibitor (ICI) response are urgently needed. This study aimed to develop a macrophage-related gene signature to predict patient outcomes and ICI efficacy, with a focus on the functional role of PLAUR. Single-cell RNA sequencing of paired HCC and normal liver tissues was used to identify macrophage subtypes. A prognostic gene signature was constructed based on macrophage-related genes and validated using the TCGA-LIHC cohort. TIDE analysis was performed to assess ICI response prediction. PLAUR-related cell communication was evaluated using CellChat. Functional assays were conducted to assess the effect of PLAUR knockdown on macrophage polarization, tumor cell behavior, and PI3K/AKT/mTOR pathway activity. Tissue microarray immunofluorescence validated PLAUR expression in situ. An eight-gene macrophage-related signature showed strong prognostic and predictive value. High-risk patients had poorer survival and reduced ICI responsiveness. PLAUR was overexpressed in tumor-associated macrophages and correlated with enhanced cell communication in tumors. Knockdown of PLAUR inhibited M2 polarization, reduced tumor cell proliferation and migration, and suppressed PI3K/AKT/mTOR signaling. In vivo, PLAUR silencing significantly reduced tumor growth in a THP-1/SKHep1 co-injection model. We identified a novel macrophage-related gene signature with clinical utility in HCC. PLAUR promotes immunosuppressive polarization and tumor progression via the PI3K/AKT/mTOR pathway, representing a potential therapeutic target and biomarker for immunotherapy response.
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