Evidence map›Paper›PMID 41268553›Full record

ArticleFrontiers in immunology2025

Machine learning-based tumor associated macrophages polarity signature predicts prognosis and treatment response in hepatocellular carcinoma.

Fangzhou Wang, Quan Zhang, Shichun Lu, Yamin Zheng

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Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Fangzhou Wang *Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China.
Quan Zhang *Department of Oncology, Xuancheng City Central Hospital, Xuancheng, Anhui, China.
Shichun LuMedical School of Chinese People's Liberation Army (PLA), Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of Chinese PLA, Key Laboratory of Digital Hepatobiliary Surgery, PLA, Beijing, China.
Yamin ZhengDepartment of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Tumor-associated macrophages (TAMs) shape the tumor microenvironment and drive hepatocellular carcinoma (HCC) progression. However, the prognostic significance of TAM polarity-related genes, particularly based on the CXCL9:SPP1 signature, remains unclear. Methods: We identified 372 TAM polarity-related genes in the TCGA-LIHC dataset. Prognostic candidates were selected using univariate Cox regression, bootstrap resampling, and the Boruta algorithm. Seven machine learning models were compared, and XGBoost was selected to construct a TAM polarity-related signature (TPS) consisting of 17 genes. TPS was validated in two external cohorts. Associations with clinical features, biological pathways, immune status, and drug sensitivity were explored. scRNA-seq and qRT-PCR were performed to investigate cellular expression and functional relevance. Results: TPS markedly different patients into high- and low-risk groups with significantly different survival outcomes (TCGA 1-, 3-, 5-year AUCs: 0.91, 0.89, 0.88). High-risk patients showed enrichment in glycan metabolism, DNA repair, and oncogenic pathways, whereas low-risk patients displayed elevated lipid and amino acid metabolism. Immune profiling revealed greater infiltration of immunosuppressive cells and higher expression of immune checkpoints in high-risk patients. Drug sensitivity analysis identified potential therapeutic targets and candidate compounds, including CDK1, PLK1, and statins. scRNA-seq analysis highlighted disrupted macrophage-immune interactions and identified SPP1 as a key signaling mediator. Silencing of TTC1 and G6PD suppressed HCC cell proliferation. Conclusion: We developed and validated a robust TAM polarity-related signature that effectively stratifies HCC patients by prognosis. TPS provides insights into tumor immunity, metabolism, and drug response, and may serve as a valuable tool for precision medicine in HCC.

Indexed as

Biomarkers, TumorCarcinoma, HepatocellularLiver NeoplasmsMachine LearningTumor-Associated MacrophagesCell PolarityFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMalePrognosisTranscriptomeTumor MicroenvironmentBiomarkers, Tumorhepatocellular carcinomamachine learningmacrophages polarityprognosissingle-cell RNA-seq

Identifiers

PMID41268553
PMCPMC12627068

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.