Molecular Characterization of Neuroendocrine-like Bladder Cancer

Area of Science:

• Oncology
• Genomics
• Molecular Pathology

Background:

• Neuroendocrine (NE) bladder carcinoma is rare and aggressive.
• 5-15% of muscle-invasive bladder cancer (MIBC) show NE transcriptomic patterns without NE histology.
• Clinical implications of this NE-like subtype are underexplored.

Purpose of the Study:

• To develop a classifier for NE-like bladder cancer.
• To investigate the clinical implications of NE-like MIBC.
• To identify a high-risk subgroup within MIBC.

Main Methods:

• Generated transcriptome-wide expression profiles for MIBC.
• Used unsupervised clustering and a random forest model to develop a single-sample classifier.
• Validated the classifier on multiple cohorts and performed survival analyses.

Main Results:

• Identified an NE-like cluster in 4.6% of the training cohort, with 1-6.6% in validation cohorts.
• NE-like tumors showed significantly worse 1-year progression-free survival (65% vs. 82%).
• Patients with NE-like tumors had a 6.4-fold increased risk of all-cause mortality (P=0.001).

Conclusions:

• Developed a classifier to identify NE-like transcriptomic profiles in histologic urothelial cancer.
• NE-like tumors represent a high-risk MIBC subgroup.
• This subgroup may require different treatment approaches.