Version 1
: Received: 26 June 2023 / Approved: 27 June 2023 / Online: 27 June 2023 (13:28:20 CEST)
How to cite:
Xiao, Y.; Zhang, T.; Wang, J.; Wang, Y.; Huo, Y. The Disulfidptosis-Mediated Intercellular Communication in the Tumor Microenvironment Contributes to the Progression of Osteosarcoma and Immunotherapy. Preprints2023, 2023061915. https://doi.org/10.20944/preprints202306.1915.v1
Xiao, Y.; Zhang, T.; Wang, J.; Wang, Y.; Huo, Y. The Disulfidptosis-Mediated Intercellular Communication in the Tumor Microenvironment Contributes to the Progression of Osteosarcoma and Immunotherapy. Preprints 2023, 2023061915. https://doi.org/10.20944/preprints202306.1915.v1
Xiao, Y.; Zhang, T.; Wang, J.; Wang, Y.; Huo, Y. The Disulfidptosis-Mediated Intercellular Communication in the Tumor Microenvironment Contributes to the Progression of Osteosarcoma and Immunotherapy. Preprints2023, 2023061915. https://doi.org/10.20944/preprints202306.1915.v1
APA Style
Xiao, Y., Zhang, T., Wang, J., Wang, Y., & Huo, Y. (2023). The Disulfidptosis-Mediated Intercellular Communication in the Tumor Microenvironment Contributes to the Progression of Osteosarcoma and Immunotherapy. Preprints. https://doi.org/10.20944/preprints202306.1915.v1
Chicago/Turabian Style
Xiao, Y., Yanan Wang and Yanqing Huo. 2023 "The Disulfidptosis-Mediated Intercellular Communication in the Tumor Microenvironment Contributes to the Progression of Osteosarcoma and Immunotherapy" Preprints. https://doi.org/10.20944/preprints202306.1915.v1
Abstract
Background: Disulfidptosis, a recently identified form of cell death triggered by excessive cysteine accumulation and subsequent disulfide stress, has emerged as a novel mechanism of cell death. Despite its significance, the role of disulfidptosis in the tumor microenvironment (TME) remains poorly understood.
Methods: In this study, we employed single-cell RNA sequencing data from 100,987 cells of 11 osteosarcoma (OS) patients. Using the non-negative matrix factorization (NMF) algorithm, we performed dimensionality reduction analysis to identify distinct subtypes characterized by 14 disulfidptosis-related genes across major cell types within the TME. Subsequently, we assessed the prognosis and immunotherapy response associated with each disulfidptosis-related subtype, leveraging publicly available databases comprising osteosarcoma data and immunotherapy cohorts.
Results: We identified distinct subtypes within tumor-associated fibroblasts, tumor-infiltrating lymphocytes, and macrophages, which we named and annotated based on their characteristic genes. Furthermore, we observed a close association between disulfidptosis-related genes and key biological features of immune cells within the TME, elucidating inferred pseudotime trajectories. Notably, integrating bulk-seq data of osteosarcoma patients, we observed significant differences in overall survival rates among the disulfidptosis-related subtypes. Particularly, the disulfidptosis-related subtype within tumor-associated fibroblasts exhibited superior discriminatory ability in predicting the response of patients undergoing immunotherapy, surpassing other cell subtypes. Our cell-cell communication analysis highlighted extensive and specific interactions between disulfidptosis-related subtypes and osteosarcoma cells. Furthermore, we confirmed the histological localization of the CAPZB+CAF subtype within osteosarcoma tissue and osteoclastoma using immunofluorescence (IF) techniques.
Conclusions: Collectively, our study sheds light on the intercellular communication facilitated by disulfidptosis in the TME, underscoring its involvement in the biological functions and immunotherapy response of osteosarcoma.
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.