Work

Based on disulfide accumulation, leveraging a THBS1-signature to improve the outcome of head and neck carcinoma patients

Year: 2025

Type: article

Abstract: Head and neck squamous cell carcinoma is a malignant cancer with specific heterogeneity. The overload of disulfide stress is a specific type of oxidative stress leading to the breakdown of the actin network and cell death. 206 proteins, which mediating the accumulation of disulfide were analyzed and quantified as the DRG score by ssGSEA. We displayed the genomics alteration landscape, the drug sensitivity to unravel the differences in copy number alterations, mutations, clinical features and immune biomarkers in diverse DRG scores. Next, we integrated 10 machine learning algorithms and 101 algorithm combinations to construct a DRG model with excellent diagnostic value, which containing 10 DRG genes. Based on these hub genes, we performed the WGCNA to identify the blue module strongly positive associated with CD4+ and CD8+ cell types, including THBS1 from blue module, CSF2, INHBA, and THBS1 from the red module. Finally, through multi-omics analyse and vitro experiments, we identified THBS1 as the core gene to inhibits disulfidptosis under glucose starvation conditions in HNSCC cells. In conclusion, our findings indicate the potential role of disulfide accumulation in HNSCC, offering new insights in the development of novel treatment strategies.

Source: International Journal of Biological Macromolecules

DOI: 10.1016/j.ijbiomac.2025.147679

Authors: Yi Jin, Zhanwang Wang, Chang Zhou, Minni Wen, Yonghong Zhou, Siwei Huang