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PANoptosis-driven molecular stratification in esophageal squamous cell carcinoma: A multi-omics prognostic model and FGFR-Targeted therapeutic validation

  • 0The Second Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi, 830011, China; Chongqing University Fuling Hospital, Chongqing, 408000, China.
Computers in Biology and Medicine +

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July 8, 2025

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July 8, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

This study developed a prognostic model for esophageal squamous cell carcinoma (ESCC) using PANoptosis-related genes. FGFR inhibitors show promise for treating high-risk ESCC by suppressing EMT and MYC/E2F pathways.

Area Of Science

  • Oncology
  • Molecular Biology
  • Immunology

Background

  • Esophageal squamous cell carcinoma (ESCC) is a deadly cancer with poor prognosis.
  • PANoptosis, a cell death pathway, is a potential biomarker for cancer prognosis and therapy.
  • The role of PANoptosis in ESCC is currently unknown.

Purpose Of The Study

  • To identify prognostic PANoptosis-related genes (PRGs) in ESCC.
  • To develop and validate a PRG-based risk model for ESCC patient stratification.
  • To explore the therapeutic potential of FGFR inhibitors in ESCC.

Main Methods

  • Univariate and LASSO Cox regression analyses for PRG identification.
  • Kaplan-Meier analysis, ROC curves, and nomograms for model validation.
  • Gene set enrichment analysis (GSEA) and single-cell RNA sequencing (scRNA-seq) for pathway and gene significance.
  • In vitro experiments to assess FGFR inhibitor efficacy.

Main Results

  • Thirteen PRGs were identified and used to construct a validated prognostic model.
  • Distinct immune microenvironment profiles were observed between high- and low-risk groups.
  • Activation of EMT, MYC signaling, and E2F targets correlated with adverse outcomes.
  • AZD4547 (FGFR inhibitor) suppressed tumor proliferation and EMT in high-risk cells.

Conclusions

  • The first prognostic model for ESCC based on PANoptosis was developed and validated.
  • FGFR inhibitors represent a promising therapeutic strategy for specific ESCC subtypes.
  • Targeting EMT and MYC/E2F pathways is crucial for effective ESCC treatment.

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