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Thomas Flaig, MD


YAP1 Activation: A Potential Prognostic and Therapeutic Factor in Bladder Cancer

By: Jenna Carter, PhD
Posted: Friday, October 21, 2022

Non–muscle-invasive bladder cancer has several available treatments; however, many patients are not responsive to these treatments, which often leads to disease progression. An article published in eBioMedicine (part of The Lancet) highlighted the use of a novel prognostic factor known to play a pivotal role in tumor progression and drug resistance. Seung-Woo Baek, PhD, of the Korea University of Science and Technology, Daejeon, and colleagues investigated distinct molecular subgroups stratified according to Yes-associated protein 1 (YAP1) activation. Their findings revealed that YAP1 activation redefined three subgroups and was associated with the characterization of patients with high-risk non–muscle-invasive bladder cancer and response to immunotherapy.

“As a clinical approach for patients with [non–muscle-invasive bladder cancer], transurethral resection followed by adjuvant intravesical therapy with Bacillus Calmette-Guérin [BCG] is recognized as the best treatment option for patients with high-risk features. However, due to the clinical heterogeneity of bladder cancer, many patients fail to respond to BCG treatment and progress to [muscle-invasive bladder cancer], indicating that effective second-line treatment options are needed,” stated Dr. Baek and colleagues.

UC3-siYAP1 cells (n = 8) and a non–muscle-invasive bladder cancer cohort (n = 460) were used to identify YAP1-associated gene signatures. A total of 1,006 patients from five independent bladder cancer cohorts were also used to cross-validate data. Cancer cells were cultured, and several genetic and Western blotting assays were used to experimentally validate the changes of gene-expression levels across each subgroup.

Findings revealed a total of 976 genes were differentially expressed among subgroups of patients with non–muscle-invasive bladder cancer in one cohort (P < .001 and 1.5-fold change). Findings also revealed that YAP1 activation redefined three subgroups, and they achieved a benefit with BCG treatment (hazard ratio = 3.32, 95% confidence interval = 1.29%–8.56%, P = .01). Furthermore, integrated analyses revealed links to high-risk cancer and responsiveness to immunotherapy.

Disclosure: The study authors reported no conflicts of interest.

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