@Article{or.2026.087891,
AUTHOR = {Zhaolong Wang, Baocheng Gong, Chaoyu Wang, Zhongyuan Li, Shuai Man, Na Lei, Jiarun Fu, Yan Jin, Benfu Zhong, Qiang Zhao},
TITLE = {Integrative Multi-Omics and Single-Cell Analyses Identify <i>FKBP10</i> as a CAF-Associated Biomarker Linked to ECM Remodeling and Aggressiveness in Neuroblastoma},
JOURNAL = {Oncology Research},
VOLUME = {},
YEAR = {},
NUMBER = {},
PAGES = {{pages}},
URL = {http://www.techscience.com/or/online/detail/28382},
ISSN = {1555-3906},
ABSTRACT = {<b>Objectives:</b> 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 <i>FKBP10</i> in NB malignant progression. <b>Methods:</b> Multi-cohort bioinformatic analyses, including weighted gene co-expression network analysis, machine learning-based <i>LASSO-Cox</i> modeling, and single-cell transcriptomics were performed to screen core stromal biomarkers. <i>In vitro</i> functional assays, rescue experiments, drug sensitivity assays, and <i>in vivo</i> xenograft models were used to validate the oncogenic role of <i>FKBP10</i> in NB. <b>Results:</b> High CAF infiltration correlated with unfavorable prognosis in NB. <i>FKBP10</i> was identified as a core stromal effector highly expressed in fibroblasts and malignant NB cells. The <i>FKBP10</i>-based signature effectively stratified patient prognosis in primary and validation cohorts. Mechanistically, <i>FKBP10</i> facilitated extracellular matrix (ECM) remodeling and mesenchymal reprogramming, accompanied by tumor immune evasion and therapeutic resistance. Functional assays demonstrated that <i>FKBP10</i> depletion suppressed NB proliferation, migration, invasion, and tumor growth, while restoring <i>FKBP10</i> rescued malignant phenotypes and reduced chemosensitivity. <b>Conclusions:</b> <i>FKBP10</i> promotes aggressive NB progression by regulating stromal activation, ECM remodeling and malignant behaviors. <i>FKBP10</i> serves as a reliable prognostic biomarker and a promising therapeutic target for high-risk neuroblastoma.},
DOI = {10.32604/or.2026.087891}
}