Integrated multi-omics profiling identifies ECM-associated and systemic metabolic alterations associated with osteosarcoma metastasis
Abstract
IntroductionOsteosarcoma metastasis remains a major clinical challenge, and the molecular programs underlying metastatic progression across omics layers are still incompletely understood.MethodsWe established an orthotopic osteosarcoma metastasis model using fluorescence-labeled 143B cells and performed integrated transcriptomic, proteomic, and serum metabolomic profiling. Multi-omics integration identified cross-layer RNA-protein-metabolite associations and prioritized hub molecules, including COL1A2, SPARC, ATP1A2, ACTA1, and MPZ. Public validation in TARGET-OS and GSE21257 supported a conserved hub/ECM co-expression module across independent cohorts. Functional assays evaluated the role of COL1A2 in osteosarcoma cell proliferation, migration, and invasion.ResultsHistological examination confirmed lung metastatic lesions in 6/6 metastasis-bearing mice but not in non-metastatic controls. Transcriptomic and proteomic profiling revealed concurrent ECM remodeling and metabolic pathway alterations. Multi-omics integration identified 32 consistently altered molecules across all three omics layers. COL1A2 was prioritized as a key hub molecule. COL1A2 knockdown promoted, whereas COL1A2 overexpression suppressed, osteosarcoma cell proliferation, migration, and Transwell invasion. Rescue experiments confirmed COL1A2-dependent regulation of these malignant phenotypes.ConclusionThese findings reveal concurrent ECM remodeling and systemic metabolic alterations associated with osteosarcoma metastasis and identify COL1A2 as a functionally relevant ECM-associated hub molecule that may serve as a potential therapeutic target.
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BibTeX
@article{liu2026integrated,
title = {{Integrated multi-omics profiling identifies ECM-associated and systemic metabolic alterations associated with osteosarcoma metastasis}},
author = {Ning Liu and Juan Wang and Yan Lai and Zhen Wu and Canhua Xu and Qin Chen and Cheng Yang},
journal = {Frontiers in Oncology},
year = {2026},
month = nov,
doi = {10.3389/fonc.2026.1956299},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1956299},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Integrated multi-omics profiling identifies ECM-associated and systemic metabolic alterations associated with osteosarcoma metastasis
AU - Ning Liu
AU - Juan Wang
AU - Yan Lai
AU - Zhen Wu
AU - Canhua Xu
AU - Qin Chen
AU - Cheng Yang
PY - 2026
DA - 2026/11/02
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1956299
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1956299
AB - IntroductionOsteosarcoma metastasis remains a major clinical challenge, and the molecular programs underlying metastatic progression across omics layers are still incompletely understood.MethodsWe established an orthotopic osteosarcoma metastasis model using fluorescence-labeled 143B cells and performed integrated transcriptomic, proteomic, and serum metabolomic profiling. Multi-omics integration identified cross-layer RNA-protein-metabolite associations and prioritized hub molecules, including COL1A2, SPARC, ATP1A2, ACTA1, and MPZ. Public validation in TARGET-OS and GSE21257 supported a conserved hub/ECM co-expression module across independent cohorts. Functional assays evaluated the role of COL1A2 in osteosarcoma cell proliferation, migration, and invasion.ResultsHistological examination confirmed lung metastatic lesions in 6/6 metastasis-bearing mice but not in non-metastatic controls. Transcriptomic and proteomic profiling revealed concurrent ECM remodeling and metabolic pathway alterations. Multi-omics integration identified 32 consistently altered molecules across all three omics layers. COL1A2 was prioritized as a key hub molecule. COL1A2 knockdown promoted, whereas COL1A2 overexpression suppressed, osteosarcoma cell proliferation, migration, and Transwell invasion. Rescue experiments confirmed COL1A2-dependent regulation of these malignant phenotypes.ConclusionThese findings reveal concurrent ECM remodeling and systemic metabolic alterations associated with osteosarcoma metastasis and identify COL1A2 as a functionally relevant ECM-associated hub molecule that may serve as a potential therapeutic target.
SN - 2234-943X
ER -