Abstract
Background
Immune checkpoint blockade (ICB) therapy has become a first-line treatment option for metastatic urothelial carcinoma (mUC) patients who do not meet the criteria of cisplatin. Still, only a few people can benefit from it, so useful predictive markers are needed.
Methods
Download the ICB-based mUC and chemotherapy-based bladder cancer cohorts, and extract the expression data of pyroptosis-related genes (PRG). The LASSO algorithm was used to construct the PRG prognostic index (PRGPI) in the mUC cohort, and we verified the prognostic ability of PRGPI in two mUC and two bladder cancer cohorts.
Results
Most of the PRG in the mUC cohort were immune-activated genes, and a few were immunosuppressive genes. The PRGPI composed of GZMB, IRF1, and TP63 can stratify the risk of mUC. In IMvigor210 and GSE176307 cohorts, the P-values of Kaplan Meier analysis was < 0.01 and 0.002, respectively. PRGPI could also predict ICB response, and the chi-square test of the two cohorts had P-values of 0.002 and 0.046, respectively. In addition, PRGPI can also predict the prognosis of two bladder cancer cohorts without ICB therapy. The PRGPI and the expression of PDCD1/CD274 had a high degree of synergistic correlation. The Low PRGPI group showed prominent characteristics of immune infiltration and was enriched in the immune signal activation pathway.
Conclusion
The PRGPI we constructed can effectively predict the treatment response and overall survival rate of mUC patients treated with ICB. The PRGPI can help mUC patients achieve individualized and accurate treatment in the future.
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Acknowledgements
This article has been presented as a preprint in the researchsquare (Lin et al. 2022) (https://www.researchsquare.com/article/rs-1625353/v1)
Funding
This work was supported by National Key Research and Development Program of China (no. 2018YFA0902802), Natural science foundation of Beijing, China (no. 7202219), National natural science foundation of China (no. 81802533), Beijing Municipal Science & Technology Commission (no. Z191100006619010).
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JL, MD, and CQ conducted data analysis and written manuscripts; YS, JH, and WY assisted in drawing pictures and collecting data; YD and TX provided ideas and designed experiments.
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Lin, J., Ding, M., Qin, C. et al. A robust gene prognostic index composed of GZMB, IRF1, and TP63 can stratify the risk of two metastatic urothelial carcinoma cohorts based on immune checkpoint blockade therapy. J Cancer Res Clin Oncol 149, 9877–9890 (2023). https://doi.org/10.1007/s00432-023-04902-z
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DOI: https://doi.org/10.1007/s00432-023-04902-z