PROX1 Expression Is Significantly Associated With ERG Expression and the TMPRSS2-ERG Fusion Gene in Prostate Cancer.

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Prostate cancer (PCa) exhibits lineage plasticity, allowing cells to evade androgen receptor (AR) dependence, leading to metastasis and treatment resistance.
• The transcription factor PROX1 drives lineage plasticity in PCa.
• The TMPRSS2-ERG fusion is a common event in PCa, associated with aggressive tumor behavior and ERG overexpression.

Purpose of the Study:

• To investigate the relationship between PROX1 expression and ERG expression in prostate cancer, specifically in the context of the TMPRSS2-ERG fusion.
• To determine if PROX1 expression correlates with ERG expression and TMPRSS2-ERG fusion status.

Main Methods:

• Analysis of The Cancer Genome Atlas (TCGA) Prostate Adenocarcinoma (PRAD) dataset (n=492).
• Utilized UCSC Xena Browser and cBioPortal for gene expression, copy number alterations, and fusion status integration.
• Assessed genomic instability and evaluated the correlation between PROX1 and ERG expression in fusion-positive and fusion-negative tumors.

Main Results:

• A strong positive correlation was observed between PROX1 and ERG expression in TMPRSS2-ERG fusion-positive prostate cancer (r=0.4, p=3.2×10^-16).
• Fusion-positive samples showed significantly higher PROX1 expression compared to fusion-negative samples.
• PROX1 induction is associated with ERG-driven transcriptional reprogramming in the context of TMPRSS2-ERG fusion.

Conclusions:

• PROX1 expression is significantly associated with ERG expression and TMPRSS2-ERG fusion status in prostate cancer.
• PROX1 serves as an early marker and potential mediator of lineage plasticity.
• Targeting PROX1 presents a potential therapeutic strategy to combat plasticity-driven progression and treatment resistance in ERG-fusion-positive prostate cancer.