Can uric acid affect the immune microenvironment in bladder cancer? A single-center multi-omics study
Haotian Chen
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, China
Search for more papers by this authorDonghui Shi
Department of Urology, Suzhou Wuzhong People's Hospital, Wuzhong, China
Search for more papers by this authorChangfeng Guo
Department of Logistic Support, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
Search for more papers by this authorWentao Zhang
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, China
Search for more papers by this authorYadong Guo
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, China
Search for more papers by this authorFuhan Yang
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, China
Search for more papers by this authorRuiliang Wang
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, China
Search for more papers by this authorJunfeng Zhang
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, China
Search for more papers by this authorZujun Fang
Department of Urology, Huashan Hospital, Fudan University, Shanghai, China
Search for more papers by this authorCorresponding Author
Yang Yan
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, China
Correspondence Xudong Yao, Shiyu Mao, and Yang Yan, Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China.
Email: [email protected], [email protected] and [email protected]
Search for more papers by this authorCorresponding Author
Shiyu Mao
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, China
Correspondence Xudong Yao, Shiyu Mao, and Yang Yan, Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China.
Email: [email protected], [email protected] and [email protected]
Search for more papers by this authorCorresponding Author
Xudong Yao
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, China
Correspondence Xudong Yao, Shiyu Mao, and Yang Yan, Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China.
Email: [email protected], [email protected] and [email protected]
Search for more papers by this authorHaotian Chen
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, China
Search for more papers by this authorDonghui Shi
Department of Urology, Suzhou Wuzhong People's Hospital, Wuzhong, China
Search for more papers by this authorChangfeng Guo
Department of Logistic Support, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
Search for more papers by this authorWentao Zhang
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, China
Search for more papers by this authorYadong Guo
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, China
Search for more papers by this authorFuhan Yang
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, China
Search for more papers by this authorRuiliang Wang
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, China
Search for more papers by this authorJunfeng Zhang
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, China
Search for more papers by this authorZujun Fang
Department of Urology, Huashan Hospital, Fudan University, Shanghai, China
Search for more papers by this authorCorresponding Author
Yang Yan
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, China
Correspondence Xudong Yao, Shiyu Mao, and Yang Yan, Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China.
Email: [email protected], [email protected] and [email protected]
Search for more papers by this authorCorresponding Author
Shiyu Mao
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, China
Correspondence Xudong Yao, Shiyu Mao, and Yang Yan, Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China.
Email: [email protected], [email protected] and [email protected]
Search for more papers by this authorCorresponding Author
Xudong Yao
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, China
Correspondence Xudong Yao, Shiyu Mao, and Yang Yan, Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China.
Email: [email protected], [email protected] and [email protected]
Search for more papers by this authorHaotian Chen, Donghui Shi, Changfeng Guo, and Wentao Zhang contributed equally to this work.
Abstract
Metabolic abnormalities are one of the important factors in bladder cancer (BCa) progression and microenvironmental disturbance. As an important product of purine metabolism, uric acid's (UA) role in BCa metabolism and immunotherapy remains unclear. In this study, we conducted a retrospective analysis of a cohort comprising 39 BCa patients treated with PD-1 and 169 patients who underwent radical cystectomy at Shanghai Tenth People's Hospital. Kaplan–Meier curves and Cox regression analysis showed that the prognosis of patients with high UA is worse (p = 0.007), and high UA is an independent risk factor for cancer specific survival in patients with BCa (p = 0.025). We established a hyperuricemia mouse model with BCa subcutaneous xenografts in vivo. The results revealed that the subcutaneous tumors of hyperuricemia mice had a greater weight and volume in comparison with the control group. Through flow cytometric analysis, the proportion of CD8+ and CD4+ T cells in these subcutaneous tumors was seen to decline significantly. We also evaluated the relationship of UA and BCa by muti-omic analysis. UA related genes were significantly increased in the CD8+ T cell of non-responders to immunotherapy by single-cell sequencing. An 11-gene UA related signature was constructed and the risk score negatively correlated with various immune cells and immune checkpoints. Finally, a nomogram was established using a UA related signature to forecast the survival rate of patients with BCa. Collectively, this study demonstrated that UA was an independent prognostic biomarker for BCa and was associated with worse immunotherapy response.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflicts of interest.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Public data that support the findings of this study are openly available in TCGA (http://cancergenome.nih.gov/), NCBI GEO dataset GSE145281 (https://www.ncbi.nlm.nih.gov/geo/). IMvigor210 with immunotherapy data and clinical information were obtained from the “IMvigor210CoreBiologies” R package. The processed data required to reproduce these findings cannot be shared at this time as the data also form part of an ongoing study. Requests to access the datasets should be directed to [email protected]. The following supporting information can be downloaded in supplement.
Supporting Information
| Filename | Description |
|---|---|
| mc23664-sup-0001-Supplementary_material.pdf2 MB | Supporting information. |
| mc23664-sup-0002-Table_S1.xlsx12.8 KB | S1 Literature collection of 208 uric acid-related genes. |
| mc23664-sup-0003-Table_S2.docx14.3 KB | Supporting information. |
| mc23664-sup-0004-Table_S3.xlsx10.5 KB | S3 37 prognostic genes were identified after univariate Cox regression analysis. |
| mc23664-sup-0005-Table_S4.docx14 KB | S4 The coefficients of the 11 hub genes. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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