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Integrative bioinformatics analysis and experimental validation identify CHEK1 as an unfavorable prognostic biomarker related to immunosuppressive phenotypes in soft tissue sarcomas

Soft tissue sarcomas (STS), including rhabdomyosarcoma (RMS), exhibit significant heterogeneity and limited responsiveness to immune checkpoint blockade (ICB). Unsupervised tumor immune phenotype based on multi-omics expression profiling of STS has been less studied. To reveal the tumor immune pheno...

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Main Authors: Rong, Chao (Author) , Liu, Yun (Author) , Xiang, Fang (Author) , Zhao, Xin (Author) , Zhang, Jinjin (Author) , Xiao, Zuorun (Author) , Wang, Jinsha (Author) , Chen, Lin (Author) , Guo, Zhiqi (Author) , Zhang, Ziyu (Author) , An, Jingnan (Author) , Shen, Jing (Author) , Heß, Jochen (Author) , Yuan, Xiaodong (Author) , Zhang, Qiong (Author) , Wang, Shouli (Author)
Format: Article (Journal)
Language:English
Published: 01 August 2025
In: npj precision oncology
Year: 2025, Volume: 9, Pages: 1-14
ISSN:2397-768X
DOI:10.1038/s41698-025-01064-8
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41698-025-01064-8
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41698-025-01064-8
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Author Notes:Chao Rong, Yun Liu, Fang Xiang, Xin Zhao, Jinjin Zhang, Zuorun Xiao, Jinsha Wang, Lin Chen, Zhiqi Guo, Ziyu Zhang, Jingnan An, Jing Shen, Jochen Hess, Xiaodong Yuan, Qiong Zhang, and Shouli Wang
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Summary:Soft tissue sarcomas (STS), including rhabdomyosarcoma (RMS), exhibit significant heterogeneity and limited responsiveness to immune checkpoint blockade (ICB). Unsupervised tumor immune phenotype based on multi-omics expression profiling of STS has been less studied. To reveal the tumor immune phenotype of STS and identify promising therapeutic targets, multi-omics expression profiling across various subtypes of STS was investigated. Here, we established a novel molecular classifier based on immune cell subsets related to TGFβ1 and IFNγ to identify distinct immune phenotypes with higher or lower cytotoxic contents. Immune-high clusters demonstrated enriched immune cell infiltration, elevated IFNγ-related signatures, and favorable clinical outcomes. In contrast, immune-low clusters were enriched for immunosuppressive cell types and exhibited poor survival. CHEK1 emerged as a key node associated with immunosuppressive phenotypes and was significantly overexpressed in immune-low tumors. In situ analysis of independent validation cohorts revealed the significant correlation between CHEK1 and tumor-infiltrating immune cells. Collectively, our findings establish a novel risk assessment strategy for RMS and STS patients, and highlight the potential of CHEK1 as a promising therapeutic target in combination with immune checkpoint inhibitor therapy.
Item Description:Gesehen am 10.12.2025
Physical Description:Online Resource
ISSN:2397-768X
DOI:10.1038/s41698-025-01064-8

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