A new study has identified a powerful biomarker that could help doctors better predict how bladder cancer behaves, and which patients are most likely to benefit from immunotherapy. The protein, known as ALYREF, appears to play a double role: it is linked to more aggressive disease, yet also signals a higher likelihood of success with immune checkpoint inhibitor (ICI) treatments.
Bladder cancer remains one of the most challenging urologic cancers to manage, largely because its course varies widely between patients. Current clinical tools often fall short in predicting both prognosis and treatment response, especially as immunotherapy becomes increasingly central to care. The discovery of ALYREF’s significance could help fill this gap.
Investigating ALYREF: Methods and Laboratory Approaches in Bladder Cancer
Researchers combined large-scale pan-cancer bioinformatic analyses with direct testing on patient samples. Using RT-qPCR, immunohistochemistry, and Western blot techniques, they measured ALYREF levels in tumour tissues and assessed how its expression related to clinical outcomes. They also analysed circulating tumour cells (CTCs), cancer cells that break away from tumours and enter the bloodstream, to explore the protein’s link to metastatic potential. Additional laboratory experiments using T24 bladder cancer cells tested whether ALYREF actively drives cancer cell movement.
ALYREF’s Dual Role: Aggressive Tumour Marker and Immunotherapy Predictor
The results were striking. ALYREF was significantly elevated in bladder cancer tissues, and high expression levels were strongly associated with more advanced tumour grade and poorer overall survival. Patients with higher ALYREF also had increased numbers of circulating tumour cells, reinforcing the protein’s connection to metastasis. In lab experiments, boosting ALYREF enhanced cancer cell migration and invasion, supporting its role in promoting tumour spread.
The study uncovered something unexpected: patients with high ALYREF expression responded better to immunotherapy, suggesting that while ALYREF marks biologically aggressive cancer, it may also indicate heightened sensitivity to ICI treatments. This duality highlights ALYREF as a potential game-changer for personalised medicine.
The researchers say ALYREF could help clinicians more precisely stratify bladder cancer patients, identifying those at higher risk of metastasis as well as those most likely to benefit from immunotherapy. Further studies are needed, but the findings offer a promising step toward more tailored, effective treatment strategies for bladder cancer patients.
Reference
Tang Z et al. Comprehensive analysis of ALYREF gene expression and its correlation with immunotherapy efficacy and circulating tumor cells in bladder cancer. Sci Rep. 2025; 15:40032
