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Published on: April 25, 2025
Integrated Single-Cell and Spatial Transcriptomics Analyses Delineate a BAG3-Associated Macrophage Program with
Ruixiang Zhang1, Yifang Wei1, Junda Yu1
1Department of Biostatistics, School of Public Health (State Key Laboratory of Multi-Organ Injury Prevention and Treatment, and Guangdong Provincial Key Laboratory of Tropical Disease Research), Southern Medical University, Guangzhou 510515, China.
This study identifies a BAG3-associated program in tumor-associated macrophages (TAMs) within hepatocellular carcinoma (HCC). This program influences the tumor microenvironment and serves as an independent prognostic factor for patient survival.
Area of Science:
- Immunology
- Oncology
- Genomics
Background:
- Tumor-associated macrophages (TAMs) are crucial in the hepatocellular carcinoma (HCC) microenvironment.
- Their spatial heterogeneity and specific functional programs remain poorly understood.
- This study investigates a BAG3-associated TAM program in HCC.
Purpose of the Study:
- To characterize the biological and prognostic significance of a BAG3-associated TAM program in HCC.
- To explore the spatial distribution and cellular interactions of TAM subsets.
- To identify potential biomarkers for HCC prognosis.
Main Methods:
- Analysis of public single-cell RNA sequencing (scRNA-seq) datasets for TAM heterogeneity.
- Spatial transcriptomics to map TAMs within the tumor microenvironment.
- Pseudotime, regulatory network, and cell-cell communication analyses to understand TAM states and interactions.
- Survival modeling to assess prognostic relevance.
Main Results:
- Five TAM subsets were identified, including a novel BAG3+ TAM subset.
- BAG3+ TAMs display coordinated stress-adaptive, proteostasis, and matrix-remodeling programs.
- Spatial mapping revealed BAG3+ TAM-enriched niches with specific transcription factor activity.
- A BAG3-associated risk score was an independent prognostic factor for overall survival in HCC patients.
Conclusions:
- A BAG3-associated TAM program has significant spatial, immunoregulatory, and prognostic relevance in HCC.
- This program involves complex crosstalk influencing the tumor microenvironment.
- The findings support further investigation of this BAG3-associated TAM program for biomarker and mechanistic studies in HCC.