Integrative Multi-Omics and Single-Cell Analyses Identify FKBP10 as a CAF-Associated Biomarker Linked to ECM Remodeling and Aggressiveness in Neuroblastoma
- 1Department of Pediatric Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
Abstract
Objectives: Neuroblastoma (NB) is a heterogeneous pediatric malignancy driven by both intrinsic oncogenic programs and the stromal microenvironment. However, the critical stromal regulators associated with poor prognosis and metastasis in NB remain poorly characterized. This study aimed to identify key cancer-associated fibroblast (CAF)-related genes and to investigate the clinical significance, biological function, and molecular mechanism of FKBP10 in NB malignant progression. Methods: Multi-cohort bioinformatic analyses, including weighted gene co-expression network analysis, machine learning-based LASSO-Cox modeling, and single-cell transcriptomics were performed to screen core stromal biomarkers. In vitro functional assays, rescue experiments, drug sensitivity assays, and in vivo xenograft models were used to validate the oncogenic role of FKBP10 in NB. Results: High CAF infiltration correlated with unfavorable prognosis in NB. FKBP10 was identified as a core stromal effector highly expressed in fibroblasts and malignant NB cells. The FKBP10-based signature effectively stratified patient prognosis in primary and validation cohorts. Mechanistically, FKBP10 facilitated extracellular matrix (ECM) remodeling and mesenchymal reprogramming, accompanied by tumor immune evasion and therapeutic resistance. Functional assays demonstrated that FKBP10 depletion suppressed NB proliferation, migration, invasion, and tumor growth, while restoring FKBP10 rescued malignant phenotypes and reduced chemosensitivity. Conclusions: FKBP10 promotes aggressive NB progression by regulating stromal activation, ECM remodeling and malignant behaviors. FKBP10 serves as a reliable prognostic biomarker and a promising therapeutic target for high-risk neuroblastoma.
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BibTeX
@article{wang2026integrative,
title = {{Integrative Multi-Omics and Single-Cell Analyses Identify FKBP10 as a CAF-Associated Biomarker Linked to ECM Remodeling and Aggressiveness in Neuroblastoma}},
author = {Zhaolong Wang and Baocheng Gong and Chaoyu Wang and Zhongyuan Li and Shuai Man and Na Lei and Jiarun Fu and Yan Jin and Benfu Zhong and Qiang Zhao},
journal = {Oncology Research},
year = {2026},
month = oct,
doi = {10.32604/or.2026.087891},
url = {https://doi.org/10.32604/or.2026.087891},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Integrative Multi-Omics and Single-Cell Analyses Identify FKBP10 as a CAF-Associated Biomarker Linked to ECM Remodeling and Aggressiveness in Neuroblastoma
AU - Zhaolong Wang
AU - Baocheng Gong
AU - Chaoyu Wang
AU - Zhongyuan Li
AU - Shuai Man
AU - Na Lei
AU - Jiarun Fu
AU - Yan Jin
AU - Benfu Zhong
AU - Qiang Zhao
PY - 2026
DA - 2026/10/28
JO - Oncology Research
DO - 10.32604/or.2026.087891
UR - https://doi.org/10.32604/or.2026.087891
AB - Objectives: Neuroblastoma (NB) is a heterogeneous pediatric malignancy driven by both intrinsic oncogenic programs and the stromal microenvironment. However, the critical stromal regulators associated with poor prognosis and metastasis in NB remain poorly characterized. This study aimed to identify key cancer-associated fibroblast (CAF)-related genes and to investigate the clinical significance, biological function, and molecular mechanism of FKBP10 in NB malignant progression. Methods: Multi-cohort bioinformatic analyses, including weighted gene co-expression network analysis, machine learning-based LASSO-Cox modeling, and single-cell transcriptomics were performed to screen core stromal biomarkers. In vitro functional assays, rescue experiments, drug sensitivity assays, and in vivo xenograft models were used to validate the oncogenic role of FKBP10 in NB. Results: High CAF infiltration correlated with unfavorable prognosis in NB. FKBP10 was identified as a core stromal effector highly expressed in fibroblasts and malignant NB cells. The FKBP10-based signature effectively stratified patient prognosis in primary and validation cohorts. Mechanistically, FKBP10 facilitated extracellular matrix (ECM) remodeling and mesenchymal reprogramming, accompanied by tumor immune evasion and therapeutic resistance. Functional assays demonstrated that FKBP10 depletion suppressed NB proliferation, migration, invasion, and tumor growth, while restoring FKBP10 rescued malignant phenotypes and reduced chemosensitivity. Conclusions: FKBP10 promotes aggressive NB progression by regulating stromal activation, ECM remodeling and malignant behaviors. FKBP10 serves as a reliable prognostic biomarker and a promising therapeutic target for high-risk neuroblastoma.
SN - 0965-0407
SN - 1555-3906
ER -