Abstract
Background
Thyroid carcinoma (THCA) is a common type of cancer worldwide, and its incidence has been increasing in recent years. Disulfidptosis, a recently defined form of metabolic-related regulated cell death (RCD), has been shown to play a sophisticated role in antitumor immunity. However, its mechanisms and functions are still poorly understood and the association between disulfidptosis and the prognosis of patients with papillary thyroid carcinoma remains to be elucidated. This study aims to investigate the connection between disulfidptosis and the prognosis of thyroid cancer, while also developing a prognostic index based on disulfidptosis genes.
Materials and methods
We utilized 24 genes associated with disulfidptosis to create the classification and model. To gather data, we sourced gene expression profiles, somatic mutation information, copy number variation data, and corresponding clinical data from the TCGA database for patients with thyroid cancer. Additionally, we obtained single-cell transcriptome data GSE184362 from the Gene Expression Omnibus (GEO) database for further analysis.
Results
In this study, we utilized 24 genes associated with disulfidptosis to identify two distinct groups with different biological processes using non-negative matrix factorization (NMF). Our findings showed that Cluster 1 is associated with chemokines, interleukins, interferons, checkpoint genes, and other important components of the immune microenvironment. Moreover, cluster 1 patients with high IPS scores may be more sensitive to immunotherapy. We also provide drug therapeutic strategies for each cluster patients based on the IC50 of each drug. The Enet model was chosen as the optimal model with the highest C-index and showed that patients with high risk had a worse prognosis and weak cell-to-cell interactions in THCA. Finally, we established a nomogram model based on multivariable cox and logistic regression analyses to predict the overall survival of THCA patients.
Conclusion
This research provides new insight into the impact of disulfidptosis on THCA. Through a thorough examination of disulfidptosis, a new classification system has been developed that can effectively predict the clinical prognosis and drug sensitivity of THCA patients.
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Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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ZF, JZ: designed this project. QZ: performed the bioinformatics analysis. ZF: wrote the manuscript and supervised the project. QZ, YD, YX, XS, QC, YZ and JM: performed the data review and modified manuscript. All authors read and approved the manuscript.
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432_2023_5006_MOESM1_ESM.pdf
Supplementary file1 Figure S1. Somatic mutation, and copy number variation patterns of different clusters. (A) Waterfall chart showing the somatic mutation frequency and specific mutations of top mutation rate genes in two clusters. (B) The location and CNV level of 24 disulfidptosis related genes in the TCGA-THCA cohort. (C) The amplification and deletion calculated by GISTIC in C1. (D) The amplification and deletion calculated by GISTIC in C2. (E) The GISTIC score of patients in C1. (F) The GISTIC score of patients in C2. (PDF 3088 KB)
432_2023_5006_MOESM2_ESM.pdf
Supplementary file2 Figure S2. (A) Kaplan-Meier of GYS1 and SLC7A11 in THCA patients. (B) Kaplan-Meier of INF2, PDLIM1 and SLC3A2 in THCA patients. (PDF 461 KB)
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Feng, Z., Zhao, Q., Ding, Y. et al. Identification a unique disulfidptosis classification regarding prognosis and immune landscapes in thyroid carcinoma and providing therapeutic strategies. J Cancer Res Clin Oncol 149, 11157–11170 (2023). https://doi.org/10.1007/s00432-023-05006-4
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DOI: https://doi.org/10.1007/s00432-023-05006-4