Newswise — In a study published in the journal Genes & Diseases, researchers from Fudan University, have developed a novel urine-based prognostic model that promises to transform the management and treatment of bladder cancer.

The research team collected urine and tumor samples from 43 bladder cancer patients, examining the expression levels of PD-L1 - a key marker in immune response - on bladder cancer cells (BCCs). And the study focused on the variability of PD-L1 expression and its response to IFN-γ in bladder cancer cells (BCCs) as detected by the BC-PD-L1 platform. From 43 bladder cancer (BLCA) patients, urine and tumor samples were obtained and used for primary cell culturing. Intriguingly, PD-L1 expression, before and after treatment with IFN-γ, varied significantly among the BCCs. Moreover, the degree of PD-L1 upregulation post-IFN-γ treatment showed a negative correlation with baseline PD-L1 expression levels. To ensure BC-PD-L1's reliability, the study employed RNA sequencing and correlated PD-L1 protein levels with mRNA levels, which validated its ability to detect PD-L1 regardless of its heavy glycosylation - a trait that can potentially obstruct accurate detection. In evaluating the platform's clinical potential, the study delved into how BC-PD-L1, especially urine-derived BC-PD-L1 (UBC-PD-L1), can predict BLCA patient outcomes. Although prior research on the prognostic significance of PD-L1 in bladder cancer has been mixed, this study's analysis revealed that higher surface PD-L1 levels were associated with longer disease-free survival and overall survival rates. Intriguingly, RNA sequencing highlighted differences between high and low PD-L1 expressing BCCs. High PD-L1 BCCs showed upregulation of pathways related to the extracellular matrix (ECM) - a key component influencing cancer progression. Additionally, these high PD-L1 BCCs were more immune-active, suggesting a better prognosis. This finding underscores the importance of PD-L1 as a potential biomarker and the BC-PD-L1's potential role in personalizing bladder cancer treatment strategies.

The study underscores the power of personalized medicine, highlighting the potential of urine-based tests in transforming bladder cancer treatments. Given bladder cancer's propensity for recurrence and the invasive nature of current diagnostic and treatment methods, this innovation offers a beacon of hope.

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References

DOI

10.1016/j.gendis.2022.10.022

Original Source URL

https://doi.org/10.1016/j.gendis.2022.10.022

Funding information

The National Natural Science Foundation of China (82073413 to S.J.),
The Clinical and Research Fund of Wu Jieping Medical Foundation (320.6750.2020-01-12 to S.J.), The National Natural Science Foundation of China (22137002 to Y.D.),
The China Postdoctoral Science Foundation ( 2020TQ0068 to J.W.).

About Genes & Diseases

Genes & Diseases is a journal for molecular and translational medicine. The journal primarily focuses on publishing investigations on the molecular bases and experimental therapeutics of human diseases. Publication formats include full length research article, review article, short communication, correspondence, perspectives, commentary, views on news, and research watch.

Journal Link: Genes & Diseases

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Genes & Diseases

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