Construction and Validation of A Risk Model for Predicting Prognosis and Immunotherapy Response of Bladder Cancer Based on Cellular Senescence-related Genes

ZHANG Peng; YANG Qian; YI Dongfeng

doi:10.3971/j.issn.1000-8578.2023.22.1214

Cancer Research on Prevention and Treatment > 2023 > 50(4): 384-389. > DOI: 10.3971/j.issn.1000-8578.2023.22.1214

ZHANG Peng, YANG Qian, YI Dongfeng. Construction and Validation of A Risk Model for Predicting Prognosis and Immunotherapy Response of Bladder Cancer Based on Cellular Senescence-related Genes[J]. Cancer Research on Prevention and Treatment, 2023, 50(4): 384-389. DOI: 10.3971/j.issn.1000-8578.2023.22.1214

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Construction and Validation of A Risk Model for Predicting Prognosis and Immunotherapy Response of Bladder Cancer Based on Cellular Senescence-related Genes

1.
Department of Urology, Guizhou Provincial People's Hospital, Guiyang 550002, China
2.
Department of Gastroenterology, Guizhou Provincial People's Hospital, Guiyang 550002, China
3.
Department of Urology, Lichuan People's Hospital, Lichuan 445400, China

Funding:

Science and Technology Fund Project of Guizhou Provincial Health Commission gzwjkj2023-369

Guizhou Provincial Science and Technology Projects QKH JC-ZK[2023]-207

More Information

Corresponding author:
YI Dongfeng, E-mail: 1460606584@qq.com
Received Date: October 16, 2022
Revised Date: November 10, 2022
Available Online: January 12, 2024

Graphical Abstract

Abstract

Abstract

Objective
To evaluate the prognosis and immunotherapy response of patients with bladder cancer by constructing a risk-score model of cellular senescence-related signature (SRS), as well as to explore the clinical application value of SRS in bladder cancer.
Methods
Senescence genes were screened from TCGA-BLCA, and cellular SRS genes were screened according to LASSO regression. A bladder cancer risk-score model was constructed based on the SRS genes to analyze the survival difference and model-fit degree of TCGA-BLCA high- and low-risk groups. Univariable and multivariable Cox regression was used to analyze the prognostic risk factors of bladder cancer. Overall survival differences of high- and low-risk groups in GEO-BLCA database were verified, and variations in immunotherapy responses were analyzed in IMvigor210 databases. According to the result of β-gal chromogenic reaction in bladder cancer and normal paracancer tissues, the existence of cell senescence was determined.
Results
Eight marker genes were screened, and patients were divided into high- and low-risk groups according to the median risk score constructed by the marker genes. The 5-year survival rate of high risk group was lower than that of low risk group (training and validation sets P < 0.05). The area under the ROC curve of TCGA-BLCA in 1-, 3-, and 5-year were 0.657, 0.660, and 0.688, and those for GSE13507 were 0.665, 0.665, and 0.613, respectively. SRS risk score can be used as an independent risk factor for the prognosis of patients with bladder cancer. The SRS risk score in the response group was lower than that in the non-response group during bladder cancer immunotherapy (P < 0.05). The β-gal staining of bladder cancer tissue was positive, but the β-gal staining of adjacent normal tissue was negative.
Conclusion
Cell senescence occurs in bladder cancer tissues. SRS risk score can predict the clinical prognosis of patients with bladder cancer, and patients with low score can benefit from immunotherapy. SRS is a reliable biomarker for the prognosis and immunotherapy response of bladder cancer.
- Bladder cancer,
- Senescence,
- Senescence-related secretion phenotype,
- Tumor microenvironment,
- Immunotherapy

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Competing interests: The authors declare that they have no competing interests.

References (22)

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Construction and Validation of A Risk Model for Predicting Prognosis and Immunotherapy Response of Bladder Cancer Based on Cellular Senescence-related Genes