Introduction: Muscle-invasive bladder cancer (MIBC) is highly heterogeneous with distinct molecular subtypes. We aimed to investigate the heterogeneity of different molecular subtypes from a tumor microenvironment perspective and develop a model to predict the molecular subtype, prognosis and immunotherapy response.
Methods: MIBC patients in The Cancer Genome Atlas (TCGA) and IMvigor210 were classified into luminal and basal subtypes according to the UNC classification. The proportions of tumor-infiltrating immune cells (TIICs) were evaluated through The Cell Type Identification by Estimating Relative Subsets of RNA Transcripts algorithm. Immune-related genes that were differently expressed between luminal and basal subtypes and associated with prognosis were selected to develop the immune prognostic signature (IPS). Nomogram based on the IPS was developed. Functional enrichment analysis (GSEA) was performed on the IPS. In addition, the RNA-sequence data of ten MIBC samples in our center were utilized to validate hub genes expression between molecular subtypes.
Results: Half of TIICs were differently distributed between luminal and basal subtypes. The IPS was highly associated with molecular subtypes, critical immune checkpoint genes expression, prognoses and immunotherapy response. Several validation data sets (GSE32894, GSE31684, GSE13507 and GSE48277) and meta-analysis further validated the prognostic value of IPS. GSEA revealed that some oncogenic pathways were coenriched in the high risk group. An IPS-based nomogram was constructed for prognostic predictions with good calibration and clinical usefulness. The expression of hub genes was significantly different between luminal and basal subtypes in MIBC samples from our center.
Conclusion: Dysregulation of TIICs contributed to the heterogeneity between luminal and basal subtypes. The IPS can facilitate molecular subtyping, prognostic evaluation and personalized immunotherapy.

Development and validation of a molecular subtype-associated immune prognostic signature for muscle invasive bladder cancer

For 2021, our focus remains: turning new data into your daily practice. The programme will consist of state-of-the-art lectures, case discussions and panel debates. Our faculty is a group of international & multidisciplinary experts.

We will take you on our journey to Ghent and beyond. Prior the congress, we send out case challenges, where you can compare your opinion with peers & experts. These cases will be part of the Global Congresses on Prostate & Bladder Cancer programme during the congress days (12 & 13 October for PROSCA and 14 & 15 October for BLADDR). After these days, you will be updated on prostate & bladder cancer management.