KRT23 Identified as Key Target in BLCA Immunotherapy

September, 09, 2024 | Bladder Cancer, Genitourinary Cancer

KEY TAKEAWAYS

  • The study aimed to investigate multiple immune checkpoint gene profiles in BLCA to identify potential immunotherapy targets like KRT23.
  • Researchers identified KRT23 as a key target for improving immunotherapy in BLCA.

In recent decades, significant progress has been made in treating bladder cancer (BLCA), particularly with the development of immune checkpoint inhibitors (ICIs). However, most studies have focused on individual ICIs, with limited research addressing the comprehensive gene expression profiles of multiple immune checkpoints. Understanding the broader landscape of immune checkpoint genes is crucial for optimizing immunotherapy strategies and improving patient outcomes.

Dongshan Chen and the team aimed to assess the expression profiles of multiple immune checkpoint genes in BLCA, explore their relationship with the tumor immune microenvironment, and identify key targets for enhancing immunotherapy, with a specific focus on KRT23.

They performed an inclusive analysis using RNA-sequencing profiling data and clinical information from patients with BLCA and normal human bladder samples, sourced from the Cancer Genome Atlas and Gene Expression Omnibus databases.

The data were analyzed to identify differential expression profiles of immune checkpoint genes (ICGs) following consensus clustering analysis. From 526 intersecting differentially expressed genes, LASSO Cox regression analysis was applied to develop an ICG signature, enabling further investigation of immune infiltration and potential therapeutic targets.

Based on the expression of ICGs, patients with BLCA were classified into 3 distinct subtypes, each exhibiting unique phenotypic and mechanistic characteristics. Furthermore, the developed ICG signature was identified as an independent predictor of outcomes in patients with BLCA and was closely associated with immune infiltration, ICG expression levels, and chemotherapy effectiveness.

The study concluded that a systematic and comprehensive analysis of immune checkpoint gene expression led to the establishment of the ICG signature, which revealed significant differences in ICG expression and the tumor immune microenvironment.

This information aids in risk stratification and supports the advancement of precision medicine for BLCA. Furthermore, KRT23 was identified as the most critical model gene, highlighting its potential as a promising target to enhance immunotherapy in patients with BLCA.

The study received no funds.

Source: https://pubmed.ncbi.nlm.nih.gov/39160525/

Chen D, Cao H, Zheng X, et al. (2024). “Immune checkpoint gene signature assesses immune infiltration profiles in bladder cancer and identifies KRT23 as an immunotherapeutic target.” BMC Cancer. 2024;24(1):1024. Published 2024 Aug 19. doi:10.1186/s12885-024-12790-w

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