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An Interferon-Response Transcriptomic Signature of Lymphovascular Invasion in Prostate Cancer.

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Lymphovascular invasion (LVI) in prostate cancer is linked to interferon signaling pathways. This finding offers new prognostic insights and potential therapeutic targets for LVI, independent of tumor grade and stage.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • Lymphovascular invasion (LVI) is a poor prognostic indicator in prostate cancer.
  • Its molecular drivers are poorly understood due to confounding factors like tumor grade and stage.

Purpose of the Study:

  • To identify molecular drivers of LVI in prostate cancer.
  • To investigate the prognostic significance of LVI-associated gene expression profiles.
  • To explore the regulatory mechanisms of identified genes.

Main Methods:

  • Confounder-adjusted transcriptomic analysis of 403 TCGA-PRAD samples.
  • Differential gene expression analysis adjusted for Gleason score and pathological T stage.
  • Multivariable logistic and Cox proportional hazards models for biochemical recurrence-free survival.
  • Multi-omics integration (methylation and expression data).

Main Results:

  • 129 genes were independently associated with LVI after multivariable adjustment.
  • This gene set was enriched for interferon-alpha/beta signaling and antiviral response pathways.
  • A composite score from this profile predicted reduced biochemical recurrence risk (aHR=0.911, p=0.033).
  • Subtle promoter hypomethylation and methylation-expression correlations were observed for key interferon genes.

Conclusions:

  • A robust, interferon-response transcriptional profile independently defines LVI in prostate cancer.
  • This signature provides prognostic information beyond standard clinicopathological factors.
  • The findings refine the biological understanding of LVI and suggest novel therapeutic targets.