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Transcriptome-wide association studies implicate RCC1 and PHACTR4 in prostate cancer survival.

Weijia Fu1, Joseph H Rothstein2,3, Olle Melander4,5

  • 1Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

European Journal of Human Genetics : EJHG
|June 20, 2026
PubMed
Summary
This summary is machine-generated.

Researchers identified seven genes linked to prostate cancer (PrCa) survival using transcriptome-wide association studies (TWAS). Genes like RCC1 and PHACTR4 show potential as genomic markers for predicting PrCa outcomes.

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Area of Science:

  • Genomics
  • Cancer Biology
  • Statistical Genetics

Background:

  • Prostate cancer (PrCa) exhibits high heritability, yet genes influencing survival post-diagnosis are not well understood.
  • Identifying genetic factors affecting PrCa survival is crucial for improving patient outcomes and developing targeted therapies.

Purpose of the Study:

  • To identify and validate genes associated with prostate cancer-specific survival using transcriptome-wide association studies (TWAS).
  • To explore the role of gene expression in normal prostate, primary tumor, and metastatic tumor tissues in relation to PrCa survival.

Main Methods:

  • Utilized the Transcriptome-Integrated Genetic Association Resource (TIGAR) to train gene expression prediction models across different prostate tissue types.
  • Performed TWAS on the Malmö Diet and Cancer (MDC) study (discovery) and Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial (validation) datasets.
  • Analyzed associations between gene expression and PrCa-specific survival, focusing on a common locus on chromosome 1.

Main Results:

  • Identified and validated seven genes associated with prostate cancer-specific survival.
  • Two genes were identified using normal prostate tissue models, and five using metastatic tumor tissue models.
  • Elevated RCC1 expression correlated with shorter time to biochemical recurrence; higher PHACTR4 expression was linked to increased Gleason grade.

Conclusions:

  • The study identified novel genes, notably RCC1 and PHACTR4, associated with PrCa survival.
  • These findings offer potential new genomic markers for predicting prostate cancer survival.
  • Further research in diverse populations and causal inference studies are recommended.