Traditional treatments, though gradually being replaced by immune checkpoint inhibitors (ICIs), have had varied success rates with limited predictors for individual patient responses. 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.
Image source: Wang et al., Genes & Diseases 2023 (CC BY-NC-ND 4.0)
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.
Source: KeAi Publishing