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Updated: Jun 4, 2026
Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer
Published on: November 2, 2013
Identification of a clinically relevant androgen-dependent gene signature in prostate cancer
Hannelore V Heemers1, Lucy J Schmidt, Zhifu Sun
1Department of Urology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. hannelore.heemers@roswellpark.org
Abstract:
The androgen receptor (AR) is the principal target for treatment of non-organ-confined prostate cancer (PCa). Androgen deprivation therapies (ADT) directed against the AR ligand-binding domain do not fully inhibit androgen-dependent signaling critical for PCa progression. Thus, information that could direct the development of more effective ADTs is desired. Systems and bioinformatics approaches suggest that considerable variation exists in the mechanisms by which AR regulates expression of effector genes, pointing to a role for secondary transcription factors. A combination of microarray and in silico analyses led us to identify a 158-gene signature that relies on AR along with the transcription factor SRF (serum response factor), representing less than 6% of androgen-dependent genes. This AR-SRF signature is sufficient to distinguish microdissected benign and malignant prostate samples, and it correlates with the presence of aggressive disease and poor outcome. The AR-SRF signature described here associates more strongly with biochemical failure than other AR target gene signatures of similar size. Furthermore, it is enriched in malignant versus benign prostate tissues, compared with other signatures. To our knowledge, this profile represents the first demonstration of a distinct mechanism of androgen action with clinical relevance in PCa, offering a possible rationale to develop novel and more effective forms of ADT.
Insights
A new 158-gene signature involving the androgen receptor (AR) and serum response factor (SRF) identifies aggressive prostate cancer (PCa). This AR-SRF signature offers a potential target for developing more effective androgen deprivation therapies (ADTs).
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- The androgen receptor (AR) is a key target in non-organ-confined prostate cancer (PCa) treatment.
- Current androgen deprivation therapies (ADTs) targeting the AR ligand-binding domain have limitations in fully inhibiting AR signaling.
- Understanding alternative AR signaling mechanisms is crucial for developing improved PCa treatments.
Purpose of the Study:
- To identify novel molecular mechanisms of androgen action in prostate cancer.
- To discover a gene expression signature associated with aggressive PCa and treatment resistance.
- To explore potential new therapeutic targets for advanced prostate cancer.
Main Methods:
- Utilized a combination of microarray analysis and in silico (computational) approaches.
- Identified a 158-gene signature dependent on both the androgen receptor (AR) and serum response factor (SRF).
- Correlated the identified gene signature with clinical outcomes and tissue characteristics in prostate cancer samples.
Main Results:
- A distinct 158-gene AR-SRF signature was identified, representing a small fraction of androgen-dependent genes.
- This AR-SRF signature effectively distinguishes benign from malignant prostate tissues.
- The signature correlates strongly with aggressive disease, poor outcomes, and biochemical failure, outperforming other AR target gene signatures.
Conclusions:
- The AR-SRF signature represents a novel, clinically relevant mechanism of androgen action in prostate cancer.
- This finding provides a potential rationale for developing new, more effective androgen deprivation therapies.
- The identified signature may serve as a biomarker for disease aggressiveness and treatment response in PCa.
