Journal Article

DKFZ-2025-01610

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Integrative bioinformatics analysis and experimental validation identify CHEK1 as an unfavorable prognostic biomarker related to immunosuppressive phenotypes in soft tissue sarcomas.

Rong, C. ; Liu, Y. ; Xiang, F. ; Zhao, X. ; Zhang, J. ; Xiao, Z. ; Wang, J. ; Chen, L. ; Guo, Z. ; Zhang, Z. ; An, J. ; Shen, J. ; Hess, J.DKFZ* ; Yuan, X. ; Zhang, Q. ; Wang, S.

2025
Springer Nature [London]

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Please use a persistent id in citations: doi:10.1038/s41698-025-01064-8

Abstract: 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.

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Contributing Institute(s):

1. Molekulare Grundlagen von HNO-Tumoren (E221)

Research Program(s):

1. 315 - Bildgebung und Radioonkologie (POF4-315) (POF4-315)

Appears in the scientific report 2025

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