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The following is a summary of “Multi-cohort validation of Ascore: an anoikis-based prognostic signature for predicting disease progression and immunotherapy response in bladder cancer,” published in the February 2024 issue of Oncology by Xie et al.
Bladder cancer stands as the 10th most prevalent cancer globally, with prognosis declining as the disease progresses. Despite the promise shown by immune checkpoint inhibitors (ICIs) in bladder cancer therapy, identifying responsive patients remains challenging. Anoikis, a specialized cell death mechanism triggered by detachment from the extracellular matrix, is intricately linked to tumor advancement. Their study aims to investigate anoikis-based biomarkers for bladder cancer prognosis and immunotherapy stratification.
Through consensus clustering of patients from the TCGA-BLCA cohort, the researchers categorized them into two clusters based on anoikis-related genes (ARGs), revealing significant differences in survival, clinical characteristics, tumor immune environment (TIME), and potential response to ICIs between clusters. Subsequently, the researchers developed a four-gene signature, termed “Ascore,” encapsulating this gene expression pattern. Ascore emerged as a robust independent prognosticator in the TCGA-BLCA and IMvigor210 cohorts and exhibited superior predictive capability (AUC = 0.717) for bladder cancer immunotherapy response compared to conventional biomarkers like TMB and PD-L1. Furthermore, in their clinical cohorts (Gulou-Cohort1 and Gulou-Cohort2), Ascore demonstrated promising prognostic performance as a non-invasive biomarker, achieving an AUC of 0.803 and outperforming PD-L1 in forecasting immunotherapy response (AUC = 0.913). Immunohistochemistry of Ascore in patients undergoing neoadjuvant anti-PD-1 treatment revealed its correlation with pathological response to bladder cancer immunotherapy (P = 0.004).
Overall, their findings introduce Ascore as a novel and robust prognostic biomarker for bladder cancer, offering a valuable tool for refining immunotherapy decisions and advancing tailored treatment approaches in this domain.
Source: molecular-cancer.biomedcentral.com/articles/10.1186/s12943-024-01945-9
