Abstract
Purpose
Disulfidptosis is a novel type of cell death induced by disulphide stress that depends on the accumulation of cystine disulphide, causing cytotoxicity and triggering cell death. However, the direct prognostic effect and regulatory mechanism of disulfidptosis-related genes in bladder urothelial carcinoma (BLCA) remain unclear.
Methods
To explore the role of 10 disulfidptosis-related genes, the multiomic data of 10 genes were comprehensively analysed. Next, based on seven disulfidptosis-related differentially expressed genes, a novel disulfidptosis-related gene score was developed to help predict the prognosis of BLCA. Immunohistochemistry, EDU, Real-time PCR and western blot were used to verify the model.
Results
Significant functional differences were found between the high- and low-risk score groups, and samples with a higher risk score were more malignant. Furthermore, the tumour exclusion and Tumour Immune Dysfunction and Exclusion scores of the high-risk score group were higher than those of the low-risk score group. The risk score was positively correlated with the expression of immune checkpoints. Drug sensitivity analyses revealed that the low-risk score group had a higher sensitivity to cisplatin, doxorubicin, docetaxel and gemcitabine than the high-risk score group. Moreover, the expression of the TM4SF1 was positively correlated with the malignancy degree of BLCA, and the proliferation ability of BLCA cells was reduced after knockdown TM4SF1.
Conclusion
The present study results suggest that disulfidptosis-related genes influence the prognosis of BLCA through their involvement in immune cell infiltration. Thus, these findings indicate the role of disulfidptosis in BLCA and its potential regulatory mechanisms.
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Data used to support the findings of this study are available from the corresponding authors upon request.
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Acknowledgements
We sincerely thank Doctor Haojie Wang, Qiong Cao and Zhihao Wei for their help with the experimental verification process. We are particularly grateful to the MogoEdit (http://www.mogoedit.com/login) for the language polishing.
Funding
This work was supported by the Medical Science and Technology Project of Henan Province (No. LHGJ20190567) and (No. LHGJ20200582).
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SX designed the research methods. RL performed the analysis; SX and RL drafted the manuscript. QC and ZW performed the IHC. HW performed the western blot, EDU and others experiments. All authors approved the version of the manuscript to be released and agreed to be responsible for all aspects of the work.
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432_2023_5235_MOESM2_ESM.tif
Supplementary Figure 2. (A-B). GO and KEGG enriched analysis for the DEGs associated with the Disulfidptosis. (C). PPI network exhibiting the connection between the DEGs associated with the Disulfidptosis
432_2023_5235_MOESM3_ESM.tif
Supplementary Figure 3. (A)Univariate COX regression analysis for the DEGs associated with the Disulfidptosis. (B). Multivariate COX regression analysis for the DEGs associated with the Disulfidptosis. (C-F) KM survival analysis indicated the difference between low- and high-expression of SLC1A6, CLIC3, SNHG18 and AKR1B15
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Xin, S., Li, R., Su, J. et al. A novel model based on disulfidptosis-related genes to predict prognosis and therapy of bladder urothelial carcinoma. J Cancer Res Clin Oncol 149, 13925–13942 (2023). https://doi.org/10.1007/s00432-023-05235-7
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DOI: https://doi.org/10.1007/s00432-023-05235-7