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A reliable transcriptomic risk-score applicable to formalin-fixed paraffin-embedded biopsies improves outcome prediction in localized prostate cancer

  • 0Department of Diagnostics, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.
Molecular Medicine +

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February 2, 2024

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February 2, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

A new gene expression signature, ProstaTrend-ffpe, accurately predicts prostate cancer recurrence using FFPE biopsies. This tool aids in early diagnosis and clinical decision-making for prostate cancer management.

Area Of Science

  • Oncology
  • Molecular Diagnostics
  • Bioinformatics

Background

  • Prostate cancer (PCa) exhibits variable clinical behavior, necessitating accurate prognostication for treatment decisions.
  • Previous development of the ProstaTrend RNA signature relied on fresh tissue, limiting its application to formalin-fixed paraffin-embedded (FFPE) biopsies.
  • The need for a reliable diagnostic tool for routine PCa diagnostics using FFPE samples is critical.

Purpose Of The Study

  • To develop and validate a novel prognostic gene-expression signature applicable to FFPE biopsies for prostate cancer.
  • To refine the existing ProstaTrend signature to overcome FFPE-associated degradation and ensure broad applicability.
  • To assess the prognostic performance of the refined signature against existing PCa panels and correlate gene expression with cellular components.

Main Methods

  • Transcriptome-wide analysis of 176 FFPE prostate cancer biopsies to filter and refine the ProstaTrend gene signature.
  • Regression analysis to identify and exclude genes susceptible to FFPE degradation.
  • Validation using Kaplan-Meier curves and Cox-regression models in the FFPE cohort and nine independent public datasets.
  • Development of a prostate single-cell atlas to analyze gene expression in different cell types.

Main Results

  • The original ProstaTrend signature showed no significant prognostic association in FFPE biopsies due to degradation.
  • The refined ProstaTrend-ffpe signature, comprising 204 genes, demonstrated significant association with biochemical recurrence (BCR) in FFPE biopsies (p < 0.001) and independent cohorts.
  • ProstaTrend-ffpe ranked among the top-performing prognostic panels and showed correlation between tumor cell gene expression, Gleason score, and BCR.

Conclusions

  • A robust prognostic gene-expression signature (ProstaTrend-ffpe) for prostate cancer has been developed for use with FFPE biopsies.
  • This novel signature shows significant prognostic value and potential for supporting clinical decision-making in routine PCa diagnostics.
  • The findings highlight the utility of FFPE samples for developing reliable molecular diagnostic tools in oncology.

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