Integrative functional-genomics analysis identifies CCT3 as a prognostic biomarker in osteosarcoma, involving the beta-catenin/c-MYC axis in malignant progression
Abstract
ObjectiveOsteosarcoma prognosis remains challenging, and reliable molecular determinants are lacking. We integrated multi-dimensional functional genomic and transcriptomic data to construct a prognostic model and investigated the key candidate gene CCT3 in osteosarcoma malignancy.MethodsWe intersected CRISPR-Cas9 dependency genes with differentially expressed genes to derive a 64-gene candidate pool, followed by stepwise Cox regression to build a risk model. Model performance was validated in training and external cohorts. Immune microenvironment, drug sensitivity, and experimental validation were performed following CCT3 knockdown.ResultsAn 8-gene risk model was constructed and significantly stratified overall survival. The high-risk group showed lower immune scores, reduced immune-cell infiltration, and downregulation of multiple immune checkpoint genes, indicating an immune-poor phenotype. Among 7 drugs with differential sensitivity, the high-risk group was more sensitive to 6 agents, including AZ6102, while showing resistance to Entospletinib. CCT3 was overexpressed in osteosarcoma tissues and cell lines; its knockdown suppressed proliferation and clonogenicity. Mechanistically, CCT3 depletion attenuated Wnt/beta-catenin signaling and reduced stemness markers CD24 and c-MYC.ConclusionOur integrative approach establishes an effective prognostic model for osteosarcoma and identifies CCT3 as a pro-tumorigenic gene, likely through the beta-catenin/c-MYC axis, representing a promising prognostic biomarker and therapeutic vulnerability.
Related
- Single-cell and bulk transcriptomic integration identifies a four-gene prognostic score linked to immunometabolic features in osteosarcoma
- An integrative analysis of transcriptome and single-cell RNA sequencing data identifies cytoskeleton-related prognostic genes in esophageal squamous cell carcinoma
- A functional connectome identifies vulnerability to cognitive decline and Alzheimer’s disease progression
- TRIM65-BTG3-HIF-1α axis drives osteosarcoma progression via M2 macrophage polarization and angiogenesis
- Integrative genetic and transcriptomic analysis identifies candidate genes and compounds for Fragile X syndrome and autism spectrum disorder
BibTeX
@article{xu2026integrative,
title = {{Integrative functional-genomics analysis identifies CCT3 as a prognostic biomarker in osteosarcoma, involving the beta-catenin/c-MYC axis in malignant progression}},
author = {Jiangbao Xu and Shengkun Hong and Zhuo Zhang and Wei Wang and Ankai Xu},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1978392},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1978392},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Integrative functional-genomics analysis identifies CCT3 as a prognostic biomarker in osteosarcoma, involving the beta-catenin/c-MYC axis in malignant progression
AU - Jiangbao Xu
AU - Shengkun Hong
AU - Zhuo Zhang
AU - Wei Wang
AU - Ankai Xu
PY - 2026
DA - 2026/11/11
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1978392
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1978392
AB - ObjectiveOsteosarcoma prognosis remains challenging, and reliable molecular determinants are lacking. We integrated multi-dimensional functional genomic and transcriptomic data to construct a prognostic model and investigated the key candidate gene CCT3 in osteosarcoma malignancy.MethodsWe intersected CRISPR-Cas9 dependency genes with differentially expressed genes to derive a 64-gene candidate pool, followed by stepwise Cox regression to build a risk model. Model performance was validated in training and external cohorts. Immune microenvironment, drug sensitivity, and experimental validation were performed following CCT3 knockdown.ResultsAn 8-gene risk model was constructed and significantly stratified overall survival. The high-risk group showed lower immune scores, reduced immune-cell infiltration, and downregulation of multiple immune checkpoint genes, indicating an immune-poor phenotype. Among 7 drugs with differential sensitivity, the high-risk group was more sensitive to 6 agents, including AZ6102, while showing resistance to Entospletinib. CCT3 was overexpressed in osteosarcoma tissues and cell lines; its knockdown suppressed proliferation and clonogenicity. Mechanistically, CCT3 depletion attenuated Wnt/beta-catenin signaling and reduced stemness markers CD24 and c-MYC.ConclusionOur integrative approach establishes an effective prognostic model for osteosarcoma and identifies CCT3 as a pro-tumorigenic gene, likely through the beta-catenin/c-MYC axis, representing a promising prognostic biomarker and therapeutic vulnerability.
SN - 1664-3224
ER -