KEY TAKEAWAYS
- The study aimed to investigate the prognostic value of M2 macrophages and their associated markers in PCa.
- Researchers noticed that M2 macrophages and their associated genes are crucial predictors of PCa progression and metastasis.
Prostate cancer (PCa) is the highest malignant tumor among men globally, with the tumor microenvironment (TME) playing a critical role in tumor growth. M2 macrophages are implicated in the progression of various solid tumors, including PCa.
Yitian Ou and the team aimed to assess the role of M2 macrophages and their associated genes in predicting the occurrence, development, and metastasis of PCa.
They performed an inclusive analysis using Single-cell RNA-seq (scRNA-seq) and mRNA expression data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Quality control, normalization, reduction, clustering, and cell annotation of scRNA-seq data were conducted using the Seurat package.
Tumor-associated macrophages (TAMs) were analyzed to identify sub-populations and marker genes specific to M2 macrophages. Differentially expressed genes (DEGs) in PCa were determined with limma, and immune infiltration was assessed using CIBERSORTx.
A weighted correlation network analysis (WGCNA) was performed to identify M2 macrophage-related modules and genes. Marker genes from scRNA-seq data and hub genes from WGCNA were integrated to develop a prognostic gene signature using Univariate and LASSO regression analyses.
The risk score was calculated, and DEGs, biological functions, and immune characteristics related to the risk score were explored. Additionally, a predictive nomogram was constructed, and CCK8, Transwell, and wound healing assays were employed to validate cell phenotype changes in co-cultured patients.
About 2,431 marker genes of M2 macrophages and 650 hub M2 macrophage-related genes were identified through scRNA-seq data and WGCNA. An overlap of scRNA-seq data and WGCNA results yielded 113 M2 macrophage-related genes. Nine M2 macrophage-related genes (SMOC2, PLPP1, HES1, STMN1, GPR160, ABCG1, MAZ, MYC, and EPCAM) were selected as prognostic gene signatures.
The M2 risk score was calculated, and DEGs, immune scores, stromal scores, ESTIMATE scores, tumor purity, immune cell infiltration, immune checkpoint expression, and responses to immunotherapy and chemotherapy were assessed. Additionally, a predictive nomogram was constructed. CCK8, Transwell invasion, and wound healing assays further confirmed that M2 macrophages promoted the proliferation, invasion, and migration of PCa (P < 0.05).
The study concluded that M2 macrophages and their associated genes are crucial in promoting the occurrence, development, and metastasis of PCa, serving as reliable predictors for the disease.
The study was funded by the Natural Science Foundation of China (No. 81860453), the Yunnan Provincial Major Science and Technology Projects (No. 2018ZF009), and the Top Physician Project of Yunnan 2019. The Scientific Research Foundation Project of Yunnan Provincial Department of Education (2022Y195), and the Project of Yunnan Provincial Science and Technology (202301AT070321, 202201AY070001-119).
Source: https://pubmed.ncbi.nlm.nih.gov/39221762/
Ou Y, Xia C, Ye C, et al. (2024). “Comprehensive scRNA-seq analysis to identify new markers of M2 macrophages for predicting the prognosis of prostate cancer.” Ann Med. 2024;56(1):2398195. doi:10.1080/07853890.2024.2398195
