JoVE - Journal of Visualized Experiments
JoVE Visualize
Contact Us

Comprehensive single-cell transcriptomic profiling reveals molecular subtypes and prognostic biomarkers with implications for targeted therapy in esophageal squamous cell carcinoma

  • 0Department of Thoracic Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China.
Translational Oncology +

|

April 6, 2024

|

April 6, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Researchers identified DNA replication stress (DRS) biomarkers in esophageal squamous cell carcinoma (ESCC). A high DRS score and specific gene signatures predict poor survival, offering new avenues for risk stratification and treatment in ESCC patients.

Area Of Science

  • Oncology
  • Genomics
  • Molecular Biology

Background

  • Esophageal squamous cell carcinoma (ESCC) is a complex cancer with poor outcomes.
  • Identifying biomarkers for DNA replication stress (DRS) is crucial for prognosis and treatment.
  • Understanding ESCC's genetic heterogeneity is key to improving patient care.

Purpose Of The Study

  • To define molecular determinants and subtypes of ESCC using integrated single-cell RNA sequencing.
  • To identify prognostic biomarkers associated with DNA replication stress in ESCC.
  • To stratify patients and guide therapeutic decisions for ESCC.

Main Methods

  • Single-cell RNA sequencing of ESCC samples analyzed with Seurat.
  • Differential gene expression analysis to identify cell phenotypes and prognostic genes.
  • Development of a DNA replication stress (DRS) score and evaluation via survival analysis, Cox regression, and clustering.

Main Results

  • A high DRS score correlated with significantly poorer survival in ESCC patients.
  • Four genes (CDKN2A, NUP155, PPP2R2A, PRKCB) demonstrated prognostic value.
  • Three distinct molecular subtypes with unique survival and immune profiles were identified; a 12-gene signature showed strong prognostic performance.

Conclusions

  • Integrated single-cell analysis reveals critical insights into ESCC heterogeneity and prognostic factors.
  • Identified prognostic biomarkers and a gene signature can enhance patient risk stratification in ESCC.
  • Experimental validation of PRKCB highlights its potential clinical utility in ESCC treatment.

Keywords: