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

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Title: Multi-omics analysis of copper metabolism-related molecular subtypes and risk stratification for osteosarcoma
Authors: Yang Zhang, Wen Liu, Dayong Liu, Xiaopeng Li, Qingshan Zhuang, Quan Sun, Xiaolin Wu, Feng Li
Source: Discover Oncology, Vol 16, Iss 1, Pp 1-17 (2025)
Publisher Information: Springer, 2025.
Publication Year: 2025
Collection: LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Subject Terms: Osteosarcoma, Copper metabolism, Immune microenvironment, Single-cell sequencing, APOA4, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2730-6011
Relation: https://doaj.org/toc/2730-6011
DOI: 10.1007/s12672-025-02273-0
Access URL: https://doaj.org/article/5cff34b45d7c4501a3e72a750cb42fd4
Accession Number: edsdoj.5cff34b45d7c4501a3e72a750cb42fd4
Database: Directory of Open Access Journals
Description
Abstract: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.
ISSN:27306011
DOI:10.1007/s12672-025-02273-0