Multi-omics analysis of copper metabolism-related molecular subtypes and risk stratification for osteosarcoma

Abstract Background As the most common primary malignant bone tumor, further investigation into risk stratification for osteosarcoma (OS) prognosis is of significant clinical importance. Copper is essential for bone metabolism; however, its specific role in OS remains unclear. Methods The expression...

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Main Authors: Yang Zhang, Wen Liu, Dayong Liu, Xiaopeng Li, Qingshan Zhuang, Quan Sun, Xiaolin Wu, Feng Li
Format: Article
Language:English
Published: Springer 2025-04-01
Series:Discover Oncology
Subjects:
Online Access:https://doi.org/10.1007/s12672-025-02273-0
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author Yang Zhang
Wen Liu
Dayong Liu
Xiaopeng Li
Qingshan Zhuang
Quan Sun
Xiaolin Wu
Feng Li
author_facet Yang Zhang
Wen Liu
Dayong Liu
Xiaopeng Li
Qingshan Zhuang
Quan Sun
Xiaolin Wu
Feng Li
author_sort Yang Zhang
collection DOAJ
description Abstract Background As the most common primary malignant bone tumor, further investigation into risk stratification for osteosarcoma (OS) prognosis is of significant clinical importance. Copper is essential for bone metabolism; however, its specific role in OS remains unclear. Methods The expression characteristics of copper metabolism related genes (CORGs) in OS were revealed by single cell sequencing. Prognosis-associated CORGs were identified, and a CORG-related scoring system and risk model were established using bioinformatics approaches, including univariate and multivariate Cox regression analyses and LASSO analysis. We further analyzed immune microenvironment infiltration, molecular subtypes and clinicopathological characteristics. The impact of selected CORG with high-risk coefficient on OS cells was tested by qRT-PCR, western blot, siRNA, colony formation analysis and Transwell in vitro. Results We successfully developed an OS scoring system related to copper metabolism and validated its independent prognostic value in patients with OS. The potential clinical value of CORG scoring system was analyzed. APOA4 was selected for in vitro experiments and its effect on the proliferation and invasion ability of OS cells was verified. Conclusion We established a copper metabolism-related scoring system to effectively stratify the risk of OS patients. Our results provide a new basis for the role of copper metabolism in OS and provide new potential targets for the treatment of OS.
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spelling doaj-art-5cff34b45d7c4501a3e72a750cb42fd42025-08-20T02:11:42ZengSpringerDiscover Oncology2730-60112025-04-0116111710.1007/s12672-025-02273-0Multi-omics analysis of copper metabolism-related molecular subtypes and risk stratification for osteosarcomaYang Zhang0Wen Liu1Dayong Liu2Xiaopeng Li3Qingshan Zhuang4Quan Sun5Xiaolin Wu6Feng Li7Department of Minimally Invasive Spine Surgery, Weifang People’s HospitalDepartment of Minimally Invasive Spine Surgery, Weifang People’s HospitalDepartment of Minimally Invasive Spine Surgery, Weifang People’s HospitalDepartment of Minimally Invasive Spine Surgery, Weifang People’s HospitalDepartment of Minimally Invasive Spine Surgery, Weifang People’s HospitalDepartment of Minimally Invasive Spine Surgery, Weifang People’s HospitalDepartment of Orthopedic Surgery, The Affiliated Hospital of Qingdao UniversityDepartment of Minimally Invasive Spine Surgery, Weifang People’s HospitalAbstract Background As the most common primary malignant bone tumor, further investigation into risk stratification for osteosarcoma (OS) prognosis is of significant clinical importance. Copper is essential for bone metabolism; however, its specific role in OS remains unclear. Methods The expression characteristics of copper metabolism related genes (CORGs) in OS were revealed by single cell sequencing. Prognosis-associated CORGs were identified, and a CORG-related scoring system and risk model were established using bioinformatics approaches, including univariate and multivariate Cox regression analyses and LASSO analysis. We further analyzed immune microenvironment infiltration, molecular subtypes and clinicopathological characteristics. The impact of selected CORG with high-risk coefficient on OS cells was tested by qRT-PCR, western blot, siRNA, colony formation analysis and Transwell in vitro. Results We successfully developed an OS scoring system related to copper metabolism and validated its independent prognostic value in patients with OS. The potential clinical value of CORG scoring system was analyzed. APOA4 was selected for in vitro experiments and its effect on the proliferation and invasion ability of OS cells was verified. Conclusion We established a copper metabolism-related scoring system to effectively stratify the risk of OS patients. Our results provide a new basis for the role of copper metabolism in OS and provide new potential targets for the treatment of OS.https://doi.org/10.1007/s12672-025-02273-0OsteosarcomaCopper metabolismImmune microenvironmentSingle-cell sequencingAPOA4
spellingShingle Yang Zhang
Wen Liu
Dayong Liu
Xiaopeng Li
Qingshan Zhuang
Quan Sun
Xiaolin Wu
Feng Li
Multi-omics analysis of copper metabolism-related molecular subtypes and risk stratification for osteosarcoma
Discover Oncology
Osteosarcoma
Copper metabolism
Immune microenvironment
Single-cell sequencing
APOA4
title Multi-omics analysis of copper metabolism-related molecular subtypes and risk stratification for osteosarcoma
title_full Multi-omics analysis of copper metabolism-related molecular subtypes and risk stratification for osteosarcoma
title_fullStr Multi-omics analysis of copper metabolism-related molecular subtypes and risk stratification for osteosarcoma
title_full_unstemmed Multi-omics analysis of copper metabolism-related molecular subtypes and risk stratification for osteosarcoma
title_short Multi-omics analysis of copper metabolism-related molecular subtypes and risk stratification for osteosarcoma
title_sort multi omics analysis of copper metabolism related molecular subtypes and risk stratification for osteosarcoma
topic Osteosarcoma
Copper metabolism
Immune microenvironment
Single-cell sequencing
APOA4
url https://doi.org/10.1007/s12672-025-02273-0
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AT xiaopengli multiomicsanalysisofcoppermetabolismrelatedmolecularsubtypesandriskstratificationforosteosarcoma
AT qingshanzhuang multiomicsanalysisofcoppermetabolismrelatedmolecularsubtypesandriskstratificationforosteosarcoma
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