Development of a novel centrosome-related risk signature to predict prognosis and treatment response in lung adenocarcinoma

Abstract Background Abnormalities of centrosomes, the major microtubular organizing centers of animal cells and regulators of cell cycle progression, usually accelerate tumor progression, but their prognostic value in lung adenocarcinoma (LUAD) remains insufficiently explored. Methods We collected c...

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Main Authors: Ziqiang Wang, Chao Zuo, Jiaojiao Fei, Huili Chen, Luyao Wang, Yiluo Xie, Jing Zhang, Shengping Min, Xiaojing Wang, Chaoqun Lian
Format: Article
Language:English
Published: Springer 2024-11-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-024-01615-8
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author Ziqiang Wang
Chao Zuo
Jiaojiao Fei
Huili Chen
Luyao Wang
Yiluo Xie
Jing Zhang
Shengping Min
Xiaojing Wang
Chaoqun Lian
author_facet Ziqiang Wang
Chao Zuo
Jiaojiao Fei
Huili Chen
Luyao Wang
Yiluo Xie
Jing Zhang
Shengping Min
Xiaojing Wang
Chaoqun Lian
author_sort Ziqiang Wang
collection DOAJ
description Abstract Background Abnormalities of centrosomes, the major microtubular organizing centers of animal cells and regulators of cell cycle progression, usually accelerate tumor progression, but their prognostic value in lung adenocarcinoma (LUAD) remains insufficiently explored. Methods We collected centrosome genes from the literature and identified LUAD-specific centrosome-related genes (CRGs) using the single-sample gene set enrichment analysis (ssGSEA) algorithm and weighted gene co-expression network analysis (WGCNA). Univariate Cox was performed to screen prognostic CRGs. Consistent clustering was performed to classify LUAD patients into two subgroups, and centrosome-related risk score signatures were constructed by Lasso and multivariate Cox regression to predict overall survival (OS). We further explored the correlation between CRS and patient prognosis, clinical manifestations, mutation status, tumor microenvironment, and response to different treatments. Results We constructed centrosome-associated prognostic features and verified that CRS could effectively predict 1-, 3-, and 5-year survival in LUAD patients. In addition, patients in the high-risk group exhibited elevated tumor mutational loads and reduced levels of immune infiltration, particularly of T and B cells. Patients in the high-risk group were resistant to immunotherapy and sensitive to 5-fluoropyrimidine and gefitinib. The key gene spermine synthase (SRM) is highly expressed at the mRNA and protein levels in LUAD. Discussion Our work develops a novel centrosome-related prognostic signature that accurately predicts OS in LUAD and can assist in clinical diagnosis and treatment.
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spelling doaj-art-5a07296748b643158f6a9ea6af06b1db2024-12-01T12:32:34ZengSpringerDiscover Oncology2730-60112024-11-0115112310.1007/s12672-024-01615-8Development of a novel centrosome-related risk signature to predict prognosis and treatment response in lung adenocarcinomaZiqiang Wang0Chao Zuo1Jiaojiao Fei2Huili Chen3Luyao Wang4Yiluo Xie5Jing Zhang6Shengping Min7Xiaojing Wang8Chaoqun Lian9Anhui Province Key Laboratory of Respiratory Tumor and Infectious Disease, Department of Pulmonary and Critical Care Medicine, Molecular Diagnosis Center, First Affiliated Hospital of Bengbu Medical UniversityDepartment of Clinical Laboratory, Affiliated Hospital of Guilin Medical UniversityAnhui Province Key Laboratory of Respiratory Tumor and Infectious Disease, Department of Pulmonary and Critical Care Medicine, Molecular Diagnosis Center, First Affiliated Hospital of Bengbu Medical UniversityResearch Center of Clinical Laboratory Science, Bengbu Medical UniversityDepartment of Genetics, School of Life Sciences, Bengbu Medical UniversityDepartment of Clinical Medicine, Bengbu Medical UniversityDepartment of Genetics, School of Life Sciences, Bengbu Medical UniversityAnhui Province Key Laboratory of Respiratory Tumor and Infectious Disease, Department of Pulmonary and Critical Care Medicine, Molecular Diagnosis Center, First Affiliated Hospital of Bengbu Medical UniversityAnhui Province Key Laboratory of Respiratory Tumor and Infectious Disease, Department of Pulmonary and Critical Care Medicine, Molecular Diagnosis Center, First Affiliated Hospital of Bengbu Medical UniversityResearch Center of Clinical Laboratory Science, Bengbu Medical UniversityAbstract Background Abnormalities of centrosomes, the major microtubular organizing centers of animal cells and regulators of cell cycle progression, usually accelerate tumor progression, but their prognostic value in lung adenocarcinoma (LUAD) remains insufficiently explored. Methods We collected centrosome genes from the literature and identified LUAD-specific centrosome-related genes (CRGs) using the single-sample gene set enrichment analysis (ssGSEA) algorithm and weighted gene co-expression network analysis (WGCNA). Univariate Cox was performed to screen prognostic CRGs. Consistent clustering was performed to classify LUAD patients into two subgroups, and centrosome-related risk score signatures were constructed by Lasso and multivariate Cox regression to predict overall survival (OS). We further explored the correlation between CRS and patient prognosis, clinical manifestations, mutation status, tumor microenvironment, and response to different treatments. Results We constructed centrosome-associated prognostic features and verified that CRS could effectively predict 1-, 3-, and 5-year survival in LUAD patients. In addition, patients in the high-risk group exhibited elevated tumor mutational loads and reduced levels of immune infiltration, particularly of T and B cells. Patients in the high-risk group were resistant to immunotherapy and sensitive to 5-fluoropyrimidine and gefitinib. The key gene spermine synthase (SRM) is highly expressed at the mRNA and protein levels in LUAD. Discussion Our work develops a novel centrosome-related prognostic signature that accurately predicts OS in LUAD and can assist in clinical diagnosis and treatment.https://doi.org/10.1007/s12672-024-01615-8Lung adenocarcinomaCentrosomeCRSPrognostic modelTumor microenvironment
spellingShingle Ziqiang Wang
Chao Zuo
Jiaojiao Fei
Huili Chen
Luyao Wang
Yiluo Xie
Jing Zhang
Shengping Min
Xiaojing Wang
Chaoqun Lian
Development of a novel centrosome-related risk signature to predict prognosis and treatment response in lung adenocarcinoma
Discover Oncology
Lung adenocarcinoma
Centrosome
CRS
Prognostic model
Tumor microenvironment
title Development of a novel centrosome-related risk signature to predict prognosis and treatment response in lung adenocarcinoma
title_full Development of a novel centrosome-related risk signature to predict prognosis and treatment response in lung adenocarcinoma
title_fullStr Development of a novel centrosome-related risk signature to predict prognosis and treatment response in lung adenocarcinoma
title_full_unstemmed Development of a novel centrosome-related risk signature to predict prognosis and treatment response in lung adenocarcinoma
title_short Development of a novel centrosome-related risk signature to predict prognosis and treatment response in lung adenocarcinoma
title_sort development of a novel centrosome related risk signature to predict prognosis and treatment response in lung adenocarcinoma
topic Lung adenocarcinoma
Centrosome
CRS
Prognostic model
Tumor microenvironment
url https://doi.org/10.1007/s12672-024-01615-8
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