Revealing intra-group immunotherapy response heterogeneity in metastatic urothelial carcinoma through interpretable feature extraction and spectral clustering.

ABSTRACT:

Introduction

Immune checkpoint inhibitors (ICIs) have improved outcomes in metastatic urothelial carcinoma (mUC) but clinical responses remain highly heterogenous. Traditional binary classification of response overlooks clinically relevant variability within each group but a more detailed understanding of intra-group heterogeneity may support subclass-specific therapeutic strategies.

Methods

We developed a novel analysis framework that integrates interpretable feature extraction and spectral clustering to identify patient subclasses associated with heterogeneous responses to ICIs. This method was applied to tumor transcriptomic data from the IMvigor210 cohort (n = 298), comprising mUC patients treated with atezolizumab. Interpretable features based on SHapley Additive exPlan

SUBMITTER: Nagumo Y 

PROVIDER: S-EPMC12816215 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature