Integrated single-cell and transcriptome sequencing to construct a prognostic model of M2 macrophage-related genes in prostate cancer

ObjectiveTo explore the prognostic value of M2 macrophage-related genes in prostate cancer (PCa), aiming to predict tumor prognosis more accurately and enable personalized treatment.Methods·RNA sequencing (RNA-seq) data of PCa were downloaded from The Cancer Genome Atlas (TCGA) database, and single-...

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Main Authors: TANG Kairan, FENG Chengling, HAN Bangmin
Format: Article
Language:zho
Published: Editorial Office of Journal of Shanghai Jiao Tong University (Medical Science) 2025-05-01
Series:Shanghai Jiaotong Daxue xuebao. Yixue ban
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Online Access:https://xuebao.shsmu.edu.cn/article/2025/1674-8115/1674-8115-2025-45-5-549.shtml
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author TANG Kairan
FENG Chengling
HAN Bangmin
author_facet TANG Kairan
FENG Chengling
HAN Bangmin
author_sort TANG Kairan
collection DOAJ
description ObjectiveTo explore the prognostic value of M2 macrophage-related genes in prostate cancer (PCa), aiming to predict tumor prognosis more accurately and enable personalized treatment.Methods·RNA sequencing (RNA-seq) data of PCa were downloaded from The Cancer Genome Atlas (TCGA) database, and single-cell RNA sequencing (scRNA-seq) data were obtained from the Gene Expression Omnibus (GEO) database. The immune infiltration of TCGA samples was assessed using the CIBERSORTx algorithm. Differential genes in scRNA-seq data were identified using the FindMarkers function, and immune cell subtypes were characterized. M2 macrophage-related pathways and interactions with surrounding cells were explored through Gene Set Enrichment Analysis (GSEA) and the CellChat algorithm. M2 macrophage signature genes were selected to construct a prognostic model for PCa using univariate Cox and LASSO analyses. Based on the risk model, clinical characteristics, immune suppression, drug resistance, and drug sensitivity analyses were conducted.Results·In TCGA samples, patients with high M2 macrophage infiltration exhibited significantly lower progression-free survival (PFS). scRNA-seq analysis identified multiple subpopulations of tumor microenvironment (TME) cells. M2 macrophages interacted with various immune cells in TME, contributing to an immunosuppressive microenvironment and playing a key role in tumor promotion. Based on these findings, a PCa risk model was developed, incorporating TREM2, OTOA, SIGLEC1, and PLXDC1, which showed robust predictive performance in both training and validation cohorts. Patients with higher risk scores demonstrated a more immunosuppressive TME, decreased androgen receptor (AR) signaling activity, and worse clinical characteristics, leading to poorer outcomes. Drug prediction and sensitivity analyses identified six potential therapeutic agents that may offer improved efficacy for patients with higher risk scores.Conclusion·A prognostic model based on M2 macrophage-related genes in the TME has been constructed, providing a theoretical foundation for precision treatment in PCa.
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spelling doaj-art-a03d4a1a37974c8ca8c9ab2efd3e1abd2025-08-20T02:07:27ZzhoEditorial Office of Journal of Shanghai Jiao Tong University (Medical Science)Shanghai Jiaotong Daxue xuebao. Yixue ban1674-81152025-05-0145554956110.3969/j.issn.1674-8115.2025.05.0031674-8115(2025)05-0549-13Integrated single-cell and transcriptome sequencing to construct a prognostic model of M2 macrophage-related genes in prostate cancerTANG Kairan0FENG Chengling1HAN Bangmin2Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, ChinaDepartment of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, ChinaDepartment of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, ChinaObjectiveTo explore the prognostic value of M2 macrophage-related genes in prostate cancer (PCa), aiming to predict tumor prognosis more accurately and enable personalized treatment.Methods·RNA sequencing (RNA-seq) data of PCa were downloaded from The Cancer Genome Atlas (TCGA) database, and single-cell RNA sequencing (scRNA-seq) data were obtained from the Gene Expression Omnibus (GEO) database. The immune infiltration of TCGA samples was assessed using the CIBERSORTx algorithm. Differential genes in scRNA-seq data were identified using the FindMarkers function, and immune cell subtypes were characterized. M2 macrophage-related pathways and interactions with surrounding cells were explored through Gene Set Enrichment Analysis (GSEA) and the CellChat algorithm. M2 macrophage signature genes were selected to construct a prognostic model for PCa using univariate Cox and LASSO analyses. Based on the risk model, clinical characteristics, immune suppression, drug resistance, and drug sensitivity analyses were conducted.Results·In TCGA samples, patients with high M2 macrophage infiltration exhibited significantly lower progression-free survival (PFS). scRNA-seq analysis identified multiple subpopulations of tumor microenvironment (TME) cells. M2 macrophages interacted with various immune cells in TME, contributing to an immunosuppressive microenvironment and playing a key role in tumor promotion. Based on these findings, a PCa risk model was developed, incorporating TREM2, OTOA, SIGLEC1, and PLXDC1, which showed robust predictive performance in both training and validation cohorts. Patients with higher risk scores demonstrated a more immunosuppressive TME, decreased androgen receptor (AR) signaling activity, and worse clinical characteristics, leading to poorer outcomes. Drug prediction and sensitivity analyses identified six potential therapeutic agents that may offer improved efficacy for patients with higher risk scores.Conclusion·A prognostic model based on M2 macrophage-related genes in the TME has been constructed, providing a theoretical foundation for precision treatment in PCa.https://xuebao.shsmu.edu.cn/article/2025/1674-8115/1674-8115-2025-45-5-549.shtmltumor-associated macrophageprostate cancerprognostic modeltumor microenvironment
spellingShingle TANG Kairan
FENG Chengling
HAN Bangmin
Integrated single-cell and transcriptome sequencing to construct a prognostic model of M2 macrophage-related genes in prostate cancer
Shanghai Jiaotong Daxue xuebao. Yixue ban
tumor-associated macrophage
prostate cancer
prognostic model
tumor microenvironment
title Integrated single-cell and transcriptome sequencing to construct a prognostic model of M2 macrophage-related genes in prostate cancer
title_full Integrated single-cell and transcriptome sequencing to construct a prognostic model of M2 macrophage-related genes in prostate cancer
title_fullStr Integrated single-cell and transcriptome sequencing to construct a prognostic model of M2 macrophage-related genes in prostate cancer
title_full_unstemmed Integrated single-cell and transcriptome sequencing to construct a prognostic model of M2 macrophage-related genes in prostate cancer
title_short Integrated single-cell and transcriptome sequencing to construct a prognostic model of M2 macrophage-related genes in prostate cancer
title_sort integrated single cell and transcriptome sequencing to construct a prognostic model of m2 macrophage related genes in prostate cancer
topic tumor-associated macrophage
prostate cancer
prognostic model
tumor microenvironment
url https://xuebao.shsmu.edu.cn/article/2025/1674-8115/1674-8115-2025-45-5-549.shtml
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AT fengchengling integratedsinglecellandtranscriptomesequencingtoconstructaprognosticmodelofm2macrophagerelatedgenesinprostatecancer
AT hanbangmin integratedsinglecellandtranscriptomesequencingtoconstructaprognosticmodelofm2macrophagerelatedgenesinprostatecancer