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Updated: May 28, 2026
07:25
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Insulin Pathway Changes in Localized Prostate Cancer: A Multi-Institutional Analysis.
Evan R Adler1, Anwaruddin Mohammad2, Pankaj Kumar2
1Department of Internal Medicine, University of Virginia, Charlottesville, VA 22904, USA.
Cancers
|May 27, 2026
Summary
Two prostate cancer patient groups showed distinct insulin pathway gene expression. While one group initially had worse survival, this difference vanished after accounting for other factors like tumor stage.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Prostate cancer progression to metastatic castrate-resistant disease remains a challenge.
- Epidemiological studies link elevated IGF-1, hyperinsulinemia, and metabolic syndrome to increased prostate cancer risk.
- Key insulin pathway genes (PTEN, FOXO, PIK3CA) are frequently altered in localized prostate tumors.
Purpose of the Study:
- Characterize insulin pathway gene expression in localized prostate cancer.
- Identify molecular mechanisms driving progression to metastatic disease.
- Enrich for prostate tumors with worse survival outcomes.
Main Methods:
- Utilized the Oncology Research Information Exchange Network (ORIEN) database for gene expression data.
- Performed non-negative matrix factorization (NMF) clustering on 176 insulin pathway genes.
- Conducted Gene Set Enrichment Analysis (GSEA) and Kaplan-Meier survival analysis.
Main Results:
- Identified two distinct insulin gene expression clusters (Cluster 1: n=96, Cluster 2: n=337).
- Cluster 1 showed decreased PTEN/PIK3R1 and increased AKT1/IRS1/2/FASN/IGFBP2/MTOR expression, with altered lipid metabolism and WNT pathways.
- Cluster 1 patients had higher T and N stages, increased metastasis, and chemotherapy needs, but survival differences disappeared after adjusting for confounders.
Conclusions:
- A subset of localized prostate cancers exhibits insulin pathway dysregulation.
- Initial survival disadvantages in the dysregulated group were explained by confounders like tumor stage, grade, and age.
- Mediation analysis indicated cluster status's effect on survival was independent of T or N stage, suggesting other factors influence outcomes.
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