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Updated: Jun 26, 2025
Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer
Published on: November 2, 2013
ProstaMine: a bioinformatics tool for identifying subtype-specific co-alterations associated with aggressiveness in
Michael V Orman1, Varsha Sreekanth1, Teemu D Laajala1,2
1Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
Background:
Prostate cancer is a leading cause of cancer-related deaths among men, marked by heterogeneous clinical and molecular characteristics. The complexity of the molecular landscape necessitates tools for identifying multi-gene co-alteration patterns that are associated with aggressive disease. The identification of such gene sets will allow for deeper characterization of the processes underlying prostate cancer progression and potentially lead to novel strategies for treatment.
Methods:
We developed ProstaMine to systematically identify co-alterations associated with aggressiveness in prostate cancer molecular subtypes defined by high-fidelity alterations in primary prostate cancer. ProstaMine integrates genomic, transcriptomic, and clinical data from five primary and one metastatic prostate cancer cohorts to prioritize co-alterations enriched in metastatic disease and associated with disease progression.
Results:
Integrated analysis of primary tumors defined a set of 17 prostate cancer alterations associated with aggressive characteristics. We applied ProstaMine to NKX3-1-loss and RB1-loss tumors and identified subtype-specific co-alterations associated with metastasis and biochemical relapse in these molecular subtypes. In NKX3-1-loss prostate cancer, ProstaMine identified novel subtype-specific co-alterations known to regulate prostate cancer signaling pathways including MAPK, NF-kB, p53, PI3K, and Sonic hedgehog. In RB1-loss prostate cancer, ProstaMine identified novel subtype-specific co-alterations involved in p53, STAT6, and MHC class I antigen presentation. Co-alterations impacting autophagy were noted in both molecular subtypes.
Conclusion:
ProstaMine is a method to systematically identify novel subtype-specific co-alterations associated with aggressive characteristics in prostate cancer. The results from ProstaMine provide insights into potential subtype-specific mechanisms of prostate cancer progression which can be formed into testable experimental hypotheses. ProstaMine is publicly available at: https://bioinformatics.cuanschutz.edu/prostamine.
