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Exploration of the Prognostic Value of PANoptosis-Related Genes in Bladder Cancer.

Jichao Tan1, Yanjue Wang1, Jian Huang1

  • 1Department of Urology, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, China.

American Journal of Men'S Health
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Summary
This summary is machine-generated.

This study identifies two PANoptosis molecular subtypes in bladder cancer (BC), revealing distinct survival outcomes. A nine-gene prognostic model effectively stratifies BC patient risk and highlights the tumor microenvironment

Keywords:
LASSOPANoptosisWGCNAbladder cancerimmune microenvironmentprognostic modelsingle-cell

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Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Bladder cancer (BC) remains a significant health concern with variable patient prognoses.
  • Understanding the molecular mechanisms underlying BC progression is crucial for developing effective therapeutic strategies.
  • PANoptosis, a newly defined cell death pathway, is increasingly recognized for its role in various cancers.

Purpose of the Study:

  • To systematically investigate the prognostic value and clinical significance of PANoptosis-related genes in bladder cancer.
  • To identify novel molecular subtypes and develop a robust prognostic model for BC.
  • To explore the relationship between PANoptosis genes and the tumor microenvironment in BC.

Main Methods:

  • Data integration from TCGA and GEO databases for comprehensive analysis.
  • Identification of PANoptosis molecular subtypes using unsupervised clustering.
  • Construction and validation of a nine-gene prognostic signature using Cox regression analysis.
  • Analysis of the tumor microenvironment and cell-type-specific gene expression via single-cell sequencing.
  • Experimental validation of key gene expression in BC tissues.

Main Results:

  • Two distinct PANoptosis molecular subtypes (C1 and C2) were identified, with subtype C2 associated with a more favorable prognosis.
  • A nine-gene prognostic model demonstrated significant predictive power for patient survival in both training and validation cohorts.
  • High-risk patients were characterized by an immunosuppressive tumor microenvironment, including increased Treg cells and M2 macrophages.
  • Single-cell sequencing revealed specific expression patterns of PANoptosis genes across different cell types within the tumor microenvironment.
  • Experimental validation confirmed the overexpression of KCNJ15, FASN, and ADAMTS12 in BC tissues.

Conclusions:

  • PANoptosis-related genes play a significant role in bladder cancer progression and patient outcomes.
  • The developed nine-gene prognostic model offers a valuable tool for risk stratification of BC patients.
  • Targeting PANoptosis pathways and modulating the tumor microenvironment may represent novel therapeutic avenues for BC.