Multi-omics analysis reveals a macrophage-related marker gene signature for prognostic prediction, immune landscape, genomic heterogeneity, and drug choices in prostate cancer

IntroductionMacrophages are components of the innate immune system and can play an anti-tumor or pro-tumor role in the tumor microenvironment owing to their high heterogeneity and plasticity. Meanwhile, prostate cancer (PCa) is an immune-sensitive tumor, making it essential to investigate the value...

Full description

Bibliographic Details
Main Authors: Weian Zhu, Jianjie Wu, Jiongduan Huang, Dongming Xiao, Fengao Li, Chenglun Wu, Xiaojuan Li, Hengda Zeng, Jiayu Zheng, Wenjie Lai, Xingqiao Wen
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-04-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1122670/full
_version_ 1797847163162591232
author Weian Zhu
Jianjie Wu
Jiongduan Huang
Dongming Xiao
Fengao Li
Chenglun Wu
Xiaojuan Li
Hengda Zeng
Jiayu Zheng
Wenjie Lai
Wenjie Lai
Xingqiao Wen
author_facet Weian Zhu
Jianjie Wu
Jiongduan Huang
Dongming Xiao
Fengao Li
Chenglun Wu
Xiaojuan Li
Hengda Zeng
Jiayu Zheng
Wenjie Lai
Wenjie Lai
Xingqiao Wen
author_sort Weian Zhu
collection DOAJ
description IntroductionMacrophages are components of the innate immune system and can play an anti-tumor or pro-tumor role in the tumor microenvironment owing to their high heterogeneity and plasticity. Meanwhile, prostate cancer (PCa) is an immune-sensitive tumor, making it essential to investigate the value of macrophage-associated networks in its prognosis and treatment.MethodsMacrophage-related marker genes (MRMGs) were identified through the comprehensive analysis of single-cell sequencing data from GSE141445 and the impact of macrophages on PCa was evaluated using consensus clustering of MRMGs in the TCGA database. Subsequently, a macrophage-related marker gene prognostic signature (MRMGPS) was constructed by LASSO-Cox regression analysis and grouped based on the median risk score. The predictive ability of MRMGPS was verified by experiments, survival analysis, and nomogram in the TCGA cohort and GEO-Merged cohort. Additionally, immune landscape, genomic heterogeneity, tumor stemness, drug sensitivity, and molecular docking were conducted to explore the relationship between MRMGPS and the tumor immune microenvironment, therapeutic response, and drug selection.ResultsWe identified 307 MRMGs and verified that macrophages had a strong influence on the development and progression of PCa. Furthermore, we showed that the MRMGPS constructed with 9 genes and the predictive nomogram had excellent predictive ability in both the TCGA and GEO-Merged cohorts. More importantly, we also found the close relationship between MRMGPS and the tumor immune microenvironment, therapeutic response, and drug selection by multi-omics analysis.DiscussionOur study reveals the application value of MRMGPS in predicting the prognosis of PCa patients. It also provides a novel perspective and theoretical basis for immune research and drug choices for PCa.
first_indexed 2024-04-09T18:06:49Z
format Article
id doaj.art-70eff9e9a74c446c93174b4c2b526922
institution Directory Open Access Journal
issn 1664-3224
language English
last_indexed 2024-04-09T18:06:49Z
publishDate 2023-04-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Immunology
spelling doaj.art-70eff9e9a74c446c93174b4c2b5269222023-04-14T05:32:25ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-04-011410.3389/fimmu.2023.11226701122670Multi-omics analysis reveals a macrophage-related marker gene signature for prognostic prediction, immune landscape, genomic heterogeneity, and drug choices in prostate cancerWeian Zhu0Jianjie Wu1Jiongduan Huang2Dongming Xiao3Fengao Li4Chenglun Wu5Xiaojuan Li6Hengda Zeng7Jiayu Zheng8Wenjie Lai9Wenjie Lai10Xingqiao Wen11Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Urology, Anqing First People’s Hospital of Anhui Medical University, Anqing, ChinaDepartment of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Health Care, Shenzhen Hospital, Southern Medical University, Shenzhen, ChinaDepartment of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaLaboratory of Biomaterials and Translational Medicine, Center for Nanomedicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaIntroductionMacrophages are components of the innate immune system and can play an anti-tumor or pro-tumor role in the tumor microenvironment owing to their high heterogeneity and plasticity. Meanwhile, prostate cancer (PCa) is an immune-sensitive tumor, making it essential to investigate the value of macrophage-associated networks in its prognosis and treatment.MethodsMacrophage-related marker genes (MRMGs) were identified through the comprehensive analysis of single-cell sequencing data from GSE141445 and the impact of macrophages on PCa was evaluated using consensus clustering of MRMGs in the TCGA database. Subsequently, a macrophage-related marker gene prognostic signature (MRMGPS) was constructed by LASSO-Cox regression analysis and grouped based on the median risk score. The predictive ability of MRMGPS was verified by experiments, survival analysis, and nomogram in the TCGA cohort and GEO-Merged cohort. Additionally, immune landscape, genomic heterogeneity, tumor stemness, drug sensitivity, and molecular docking were conducted to explore the relationship between MRMGPS and the tumor immune microenvironment, therapeutic response, and drug selection.ResultsWe identified 307 MRMGs and verified that macrophages had a strong influence on the development and progression of PCa. Furthermore, we showed that the MRMGPS constructed with 9 genes and the predictive nomogram had excellent predictive ability in both the TCGA and GEO-Merged cohorts. More importantly, we also found the close relationship between MRMGPS and the tumor immune microenvironment, therapeutic response, and drug selection by multi-omics analysis.DiscussionOur study reveals the application value of MRMGPS in predicting the prognosis of PCa patients. It also provides a novel perspective and theoretical basis for immune research and drug choices for PCa.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1122670/fullprostate cancermacrophage-related marker geneprognostic signaturetumor immunitygenomic heterogeneitydrug choices
spellingShingle Weian Zhu
Jianjie Wu
Jiongduan Huang
Dongming Xiao
Fengao Li
Chenglun Wu
Xiaojuan Li
Hengda Zeng
Jiayu Zheng
Wenjie Lai
Wenjie Lai
Xingqiao Wen
Multi-omics analysis reveals a macrophage-related marker gene signature for prognostic prediction, immune landscape, genomic heterogeneity, and drug choices in prostate cancer
Frontiers in Immunology
prostate cancer
macrophage-related marker gene
prognostic signature
tumor immunity
genomic heterogeneity
drug choices
title Multi-omics analysis reveals a macrophage-related marker gene signature for prognostic prediction, immune landscape, genomic heterogeneity, and drug choices in prostate cancer
title_full Multi-omics analysis reveals a macrophage-related marker gene signature for prognostic prediction, immune landscape, genomic heterogeneity, and drug choices in prostate cancer
title_fullStr Multi-omics analysis reveals a macrophage-related marker gene signature for prognostic prediction, immune landscape, genomic heterogeneity, and drug choices in prostate cancer
title_full_unstemmed Multi-omics analysis reveals a macrophage-related marker gene signature for prognostic prediction, immune landscape, genomic heterogeneity, and drug choices in prostate cancer
title_short Multi-omics analysis reveals a macrophage-related marker gene signature for prognostic prediction, immune landscape, genomic heterogeneity, and drug choices in prostate cancer
title_sort multi omics analysis reveals a macrophage related marker gene signature for prognostic prediction immune landscape genomic heterogeneity and drug choices in prostate cancer
topic prostate cancer
macrophage-related marker gene
prognostic signature
tumor immunity
genomic heterogeneity
drug choices
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1122670/full
work_keys_str_mv AT weianzhu multiomicsanalysisrevealsamacrophagerelatedmarkergenesignatureforprognosticpredictionimmunelandscapegenomicheterogeneityanddrugchoicesinprostatecancer
AT jianjiewu multiomicsanalysisrevealsamacrophagerelatedmarkergenesignatureforprognosticpredictionimmunelandscapegenomicheterogeneityanddrugchoicesinprostatecancer
AT jiongduanhuang multiomicsanalysisrevealsamacrophagerelatedmarkergenesignatureforprognosticpredictionimmunelandscapegenomicheterogeneityanddrugchoicesinprostatecancer
AT dongmingxiao multiomicsanalysisrevealsamacrophagerelatedmarkergenesignatureforprognosticpredictionimmunelandscapegenomicheterogeneityanddrugchoicesinprostatecancer
AT fengaoli multiomicsanalysisrevealsamacrophagerelatedmarkergenesignatureforprognosticpredictionimmunelandscapegenomicheterogeneityanddrugchoicesinprostatecancer
AT chenglunwu multiomicsanalysisrevealsamacrophagerelatedmarkergenesignatureforprognosticpredictionimmunelandscapegenomicheterogeneityanddrugchoicesinprostatecancer
AT xiaojuanli multiomicsanalysisrevealsamacrophagerelatedmarkergenesignatureforprognosticpredictionimmunelandscapegenomicheterogeneityanddrugchoicesinprostatecancer
AT hengdazeng multiomicsanalysisrevealsamacrophagerelatedmarkergenesignatureforprognosticpredictionimmunelandscapegenomicheterogeneityanddrugchoicesinprostatecancer
AT jiayuzheng multiomicsanalysisrevealsamacrophagerelatedmarkergenesignatureforprognosticpredictionimmunelandscapegenomicheterogeneityanddrugchoicesinprostatecancer
AT wenjielai multiomicsanalysisrevealsamacrophagerelatedmarkergenesignatureforprognosticpredictionimmunelandscapegenomicheterogeneityanddrugchoicesinprostatecancer
AT wenjielai multiomicsanalysisrevealsamacrophagerelatedmarkergenesignatureforprognosticpredictionimmunelandscapegenomicheterogeneityanddrugchoicesinprostatecancer
AT xingqiaowen multiomicsanalysisrevealsamacrophagerelatedmarkergenesignatureforprognosticpredictionimmunelandscapegenomicheterogeneityanddrugchoicesinprostatecancer