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A comprehensive analysis of immunogenic cell death and its key gene HSP90AA1 in bladder cancer

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Abstract

Background

Bladder cancer (BLCA) is defined as a type of urinary cancer with high incidence and lack of specific biomarkers and drug targets. Immunogenic cell death (ICD) has been classified as a regulated type of cell death. Growing evidence suggested that ICD can reshape the tumor immune microenvironment, which may contribute to the development of immunotherapy strategies. The aim of this study was to reveal the specific mechanism of ICD in bladder cancer and to further predict the prognostic immunotherapy outcomes.

Methods

By consensus clustering analysis, bladder cancer patients in TCGA database were divided into different ICD subtypes. Additionally, we developed an ICD-scoring system and constructed the ICD score-based risk signature and nomogram to better characterize patients. Furthermore, we carried out a series of experiments to verify the relevant findings.

Results

Based on the transcriptome expression levels of ICD-related genes, a total of 403 BLCA patients in the TCGA database were divided into two subgroups with different ICD molecular patterns by consensus cluster analysis. These subgroups showed different clinicopathological features, survival outcomes, tumor microenvironment (TME) characteristics, immune-related scores, and treatment response. Moreover, the established prediction model and ICD score can effectively distinguish high risk/score patients from low risk/score patients, which has excellent predictive value. Finally, we found that the key gene HSP90AA1 was highly expressed in the high-ICD score group and in bladder cancer tissues, and was confirmed to be associated with the proliferation of bladder cancer cells.

Conclusion

To sum up, we established a new classification system for BLCA based on ICD-related genes. This stratification has significant predictive power for clinical outcomes and can effectively evaluate the prognosis and immunotherapy of BLCA patients. Finally, it was proved that HSP90AA1 was highly expressed in BLCA and would be a promising therapeutic target for BLCA.

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Availability of data and material

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.

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Acknowledgements

We acknowledge and appreciate the help in plot from Figure Ya.

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This research received no external funding.

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Authors and Affiliations

  1. Department of Urology, The First People’s Hospital of Yancheng (Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School), No.66 South Renmin Road, Yancheng, 224000, Jiangsu, China

    Qiang Song, Zhengdong Zhou, Jinming Bai & Ning Liu

  2. Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People’s Republic of China

    Qiang Song

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  1. Qiang Song
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  2. Zhengdong Zhou
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Contributions

Data curation, Software, Writing-Original draft preparation Qiang Song; Visualization, Software, Formal analysis ZZ Writing-Review & Editing, Project administration JB; Conceptualization, Methodology, Writing-Reviewing and Editing Ning Liu. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Ning Liu.

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Song, Q., Zhou, Z., Bai, J. et al. A comprehensive analysis of immunogenic cell death and its key gene HSP90AA1 in bladder cancer. Clin Transl Oncol 25, 2587–2606 (2023). https://doi.org/10.1007/s12094-023-03143-3

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  • DOI: https://doi.org/10.1007/s12094-023-03143-3

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