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Molecular Classification of Bladder Urothelial Carcinoma Using NanoString-Based Gene Expression Analysis.

Antonio Lopez-Beltran1, Ana Blanca2, Alessia Cimadamore3

  • 1Department of Morphological Sciences, University of Cordoba Medical School, E-14004 Cordoba, Spain.

Cancers
|November 13, 2021
PubMed
Summary

A new four-gene panel effectively classifies bladder cancer into luminal, basal, and null subtypes, correlating with survival outcomes and PD-L1 expression. This accessible NanoString-based tool aids precision genomics in oncology.

Keywords:
NanoStringbasalbladder cancerclassificationluminalmolecularmolecular taxonomy

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Area of Science:

  • Oncology
  • Genomics
  • Molecular Biology

Background:

  • Molecular classification of bladder carcinoma is crucial for improving oncological outcomes.
  • Current transcriptomic classifications are complex, costly, and have limited global availability.
  • A need exists for accessible and affordable molecular classification tools in bladder cancer.

Purpose of the Study:

  • To evaluate a four-gene panel for molecular classification of bladder cancer using NanoString technology.
  • To correlate molecular subtypes with clinical outcomes, including survival and tumor stage.
  • To assess the relationship between molecular subtypes and PD-L1 expression.

Main Methods:

  • Gene expression analysis of a four-gene panel (luminal and basal markers) in 91 bladder cancer cases.
  • Classification into luminal, basal, and null/double negative subtypes using NanoString technology.
  • Statistical analysis correlating subtypes with overall survival, histology, stage, and PD-L1 expression.

Main Results:

  • Three distinct molecular subtypes (luminal, basal, null) were identified, significantly correlating with cancer-specific survival (p < 0.0001).
  • Subtypes showed significant associations with conventional vs. variant histology (p < 0.0001), NMIBC vs. MIBC (p < 0.001), and AJCC stages Ta (p = 0.0012) and T1 (p < 0.0001).
  • High PD-L1 expression was prevalent in basal and null subtypes, and variant histology (p = 0.002). Luminal subtype correlated with favorable NMIBC outcomes, while basal and null subtypes indicated aggressive MIBC.

Conclusions:

  • A four-gene classifier using NanoString technology provides a feasible, accessible, and affordable method for molecular subtyping of bladder cancer.
  • This classification system offers meaningful correlations with survival, histology, stage, and PD-L1 expression, supporting its use in precision genomics.
  • The study demonstrates the potential of this gene classifier to enhance personalized treatment strategies in bladder cancer management.