TY  - JOUR
AU  - Rong, Chao
AU  - Liu, Yun
AU  - Xiang, Fang
AU  - Zhao, Xin
AU  - Zhang, Jinjin
AU  - Xiao, Zuorun
AU  - Wang, Jinsha
AU  - Chen, Lin
AU  - Guo, Zhiqi
AU  - Zhang, Ziyu
AU  - An, Jingnan
AU  - Shen, Jing
AU  - Hess, Jochen
AU  - Yuan, Xiaodong
AU  - Zhang, Qiong
AU  - Wang, Shouli
TI  - Integrative bioinformatics analysis and experimental validation identify CHEK1 as an unfavorable prognostic biomarker related to immunosuppressive phenotypes in soft tissue sarcomas.
JO  - npj precision oncology
VL  - 9
IS  - 1
SN  - 2397-768X
CY  - [London]
PB  - Springer Nature
M1  - DKFZ-2025-01610
SP  - 268
PY  - 2025
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:40751074
C2  - pmc:PMC12317078
DO  - DOI:10.1038/s41698-025-01064-8
UR  - https://inrepo02.dkfz.de/record/303360
ER  -