Multi-omics analysis unveils a four-gene prognostic signature in esophageal squamous carcinoma and the therapeutic potential of PKP1

  • 0College of Public Health, Zhengzhou University, Zhengzhou, 4500001, China.

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Summary

This summary is machine-generated.

This study developed a four-gene signature (CCND1-PKP1-JUP-ANKRD12) to predict esophageal squamous cell carcinoma (ESCC) patient survival. PKP1 also shows potential for gene therapy in multiple cancers.

Area Of Science

  • Oncology
  • Genomics
  • Molecular Biology

Background

  • Esophageal squamous cell carcinoma (ESCC) is a heterogeneous malignancy with poor patient outcomes.
  • Accurate patient stratification and prognostic markers are essential for effective treatment strategies.

Purpose Of The Study

  • To classify ESCC subtypes using integrated single-cell and bulk RNA sequencing.
  • To develop a novel gene signature for predicting ESCC prognosis and guiding treatment decisions.

Main Methods

  • Integrated single-cell and bulk RNA sequencing (RNA-seq) for ESCC characterization.
  • Non-negative matrix factorization (NMF) for patient stratification into subtypes.
  • Cox and LASSO regression analyses to construct a four-gene prognostic risk model (CCND1-PKP1-JUP-ANKRD12).
  • Validation using RT-qPCR, proteomics, and multiplex immunohistochemistry (mIHC).

Main Results

  • Identified four distinct ESCC subtypes with unique cellular features and prognoses.
  • The CCND1-PKP1-JUP-ANKRD12 signature accurately predicted patient survival, independent of clinical factors.
  • Gene expression correlated with immunoregulatory genes and anti-cancer drug sensitivities.
  • PKP1 expression linked to EGFR levels and gene effect scores across various cancers.

Conclusions

  • The CCND1-PKP1-JUP-ANKRD12 signature offers a promising tool for ESCC prognosis and diagnosis.
  • PKP1 dysregulation presents potential therapeutic targets for gene therapy in multiple cancers.