Systematic analysis of ZDHHC9 as a potential prognostic and immunotherapy biomarker in breast cancer

BackgroundBreast cancer (BC) represents a highly heterogeneous malignancy and continues to be a leading source of death among women worldwide. Enhancing diagnostic and therapeutic approaches necessitates a thorough grasp of the underlying molecular pathways and the identification of dependable bioma...

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Main Authors: Desheng Zhou, Zhenpeng Wu, Yachao Cui, Doudou Wang, Hejun Song, Jun Chen, Hong Lin
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1609621/full
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author Desheng Zhou
Zhenpeng Wu
Yachao Cui
Yachao Cui
Doudou Wang
Hejun Song
Jun Chen
Hong Lin
author_facet Desheng Zhou
Zhenpeng Wu
Yachao Cui
Yachao Cui
Doudou Wang
Hejun Song
Jun Chen
Hong Lin
author_sort Desheng Zhou
collection DOAJ
description BackgroundBreast cancer (BC) represents a highly heterogeneous malignancy and continues to be a leading source of death among women worldwide. Enhancing diagnostic and therapeutic approaches necessitates a thorough grasp of the underlying molecular pathways and the identification of dependable biomarkers. Although palmitoyl transferases, particularly ZDHHC9, have been associated with the progression of various cancers, their specific role in BC remains incompletely understood.MethodsIn this investigation, TCGA and GTEx databases were utilized to analyze the expression patterns of ZDHHC9 and to evaluate its prognostic significance. Moreover, the regulatory pathways involving ZDHHC9 were explored via co-expression analysis and differential gene enrichment studies. Insights into ZDHHC9 expression across different cell types and its potential oncogenic pathways were derived from scRNA sequencing analysis. Additionally, immunophenoscore (IPS), EaSIeR and immunotherapy cohorts were utilized to predict immunotherapy responses. The biological significance of ZDHHC9 was verified through in vitro and in vivo experiments.ResultsOur findings revealed that ZDHHC9 is markedly overexpressed in BC, with elevated levels of ZDHHC9 being correlated with poor survival outcomes, suggesting its role as an independent risk factor in BC. Furthermore, high ZDHHC9 expression was found to be associated with multiple immune cell types within BC. Notably, patients exhibiting lower ZDHHC9 expression demonstrated a higher likelihood of benefitting from immunotherapy. Lastly, the vivo and vitro experiments consistently demonstrated that suppression of ZDHHC9 expression could reduce BC cell proliferation.ConclusionsThis study highlights ZDHHC9 as a potential prognostic marker, a regulator of tumor immunity, and a biomarker of therapeutic response in BC, offering a promising avenue for improving BC diagnosis and treatment.
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spelling doaj-art-8238dc2cd7be4eafadeb30bf49f766022025-08-20T03:13:32ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.16096211609621Systematic analysis of ZDHHC9 as a potential prognostic and immunotherapy biomarker in breast cancerDesheng Zhou0Zhenpeng Wu1Yachao Cui2Yachao Cui3Doudou Wang4Hejun Song5Jun Chen6Hong Lin7The Sixth School of Clinical Medicine, The Affiliated Qingyuan Hospital (Qingyuan People’s Hospital), Guangzhou Medical University, Qingyuan, ChinaGuangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, ChinaThe First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Health, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou, ChinaGuangzhou National Laboratory, Guangzhou, ChinaShaanxi Energy Institute, Shaanxi, ChinaGuangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, ChinaThyroid and Breast Surgery Department, Shenzhen Hospital, Southern Medicaid University, Shenzhen, ChinaThe Sixth School of Clinical Medicine, The Affiliated Qingyuan Hospital (Qingyuan People’s Hospital), Guangzhou Medical University, Qingyuan, ChinaBackgroundBreast cancer (BC) represents a highly heterogeneous malignancy and continues to be a leading source of death among women worldwide. Enhancing diagnostic and therapeutic approaches necessitates a thorough grasp of the underlying molecular pathways and the identification of dependable biomarkers. Although palmitoyl transferases, particularly ZDHHC9, have been associated with the progression of various cancers, their specific role in BC remains incompletely understood.MethodsIn this investigation, TCGA and GTEx databases were utilized to analyze the expression patterns of ZDHHC9 and to evaluate its prognostic significance. Moreover, the regulatory pathways involving ZDHHC9 were explored via co-expression analysis and differential gene enrichment studies. Insights into ZDHHC9 expression across different cell types and its potential oncogenic pathways were derived from scRNA sequencing analysis. Additionally, immunophenoscore (IPS), EaSIeR and immunotherapy cohorts were utilized to predict immunotherapy responses. The biological significance of ZDHHC9 was verified through in vitro and in vivo experiments.ResultsOur findings revealed that ZDHHC9 is markedly overexpressed in BC, with elevated levels of ZDHHC9 being correlated with poor survival outcomes, suggesting its role as an independent risk factor in BC. Furthermore, high ZDHHC9 expression was found to be associated with multiple immune cell types within BC. Notably, patients exhibiting lower ZDHHC9 expression demonstrated a higher likelihood of benefitting from immunotherapy. Lastly, the vivo and vitro experiments consistently demonstrated that suppression of ZDHHC9 expression could reduce BC cell proliferation.ConclusionsThis study highlights ZDHHC9 as a potential prognostic marker, a regulator of tumor immunity, and a biomarker of therapeutic response in BC, offering a promising avenue for improving BC diagnosis and treatment.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1609621/fullbreast cancerimmunotherapyprognosistumor microenvironmentZdhhc9
spellingShingle Desheng Zhou
Zhenpeng Wu
Yachao Cui
Yachao Cui
Doudou Wang
Hejun Song
Jun Chen
Hong Lin
Systematic analysis of ZDHHC9 as a potential prognostic and immunotherapy biomarker in breast cancer
Frontiers in Immunology
breast cancer
immunotherapy
prognosis
tumor microenvironment
Zdhhc9
title Systematic analysis of ZDHHC9 as a potential prognostic and immunotherapy biomarker in breast cancer
title_full Systematic analysis of ZDHHC9 as a potential prognostic and immunotherapy biomarker in breast cancer
title_fullStr Systematic analysis of ZDHHC9 as a potential prognostic and immunotherapy biomarker in breast cancer
title_full_unstemmed Systematic analysis of ZDHHC9 as a potential prognostic and immunotherapy biomarker in breast cancer
title_short Systematic analysis of ZDHHC9 as a potential prognostic and immunotherapy biomarker in breast cancer
title_sort systematic analysis of zdhhc9 as a potential prognostic and immunotherapy biomarker in breast cancer
topic breast cancer
immunotherapy
prognosis
tumor microenvironment
Zdhhc9
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1609621/full
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