See the published version of this article at BMC Urology.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Early upregulation of AR and steroidogenesis enzyme expression after 3 months of androgen-deprivation therapy.
Agus Rizal A.H. Hamid
Department of Urology, Cipto Mangunkusumo National Referral Hospital-University of Indonesia
Corresponding Author
ORCiD: https://orcid.org/0000-0002-7538-2811
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at BMC Urology.
Background: Androgen deprivation therapy (ADT) is a standard treatment for advanced prostate cancer (PCa). However, PCa recurrence and progression rates during ADT are high. Until now, there has been no evidence regarding when progression begins. This study evaluated the gene expression of intraprostatic androgen receptor (AR) and steroidogenic enzymes in the early stages of ADT.
Methods: Prostate tissue samples were taken from PCa patients with urinary retention who received ADT (ADT-PCa; n=10) and were further subgrouped into ADT ≤12 months (n=4) and ADT >12 months (n=6). The ADT-PCa tissues were then compared with BPH (n=12) and primary (no treatment) PCa tissues (n=16). mRNA for gene expression analysis of AR and steroidogenic enzymes was extracted from formalin-fixed paraffin embedded (FFPE) tissues and analyzed by real-time PCR. Protein expression was evaluated by immunohistochemistry with specific antibodies.
Results: AR gene expression was higher in the ADT-PCa group than in the BPH or primary PCa group. Both the ADT ≤12 and > 12 months subgroups had significantly higher relative gene expression levels of AR (p<0.01 and 0.03, respectively) than the primary PCa group. In the ADT-PCa group, AR protein expression showed an increasing trend in the ADT ≤12 months subgroup and was significantly elevated in the ADT >12 months subgroup compared with the PCa group (100%; p <0.01). Half (50%) of the patients in the ADT ≤12 months subgroup were found to have upregulation of AR, and one showed upregulation beginning at 3 months of ADT. A trend toward elevated relative gene expression of SRD5A3 was also apparent in the ADT groups.
Conclusion: AR and steroidogenic enzymes are upregulated in ADT-PCa patients as early as 3 months, without PSA elevation. Steroidogenic enzymes, particularly SRD5A3, were also upregulated before PSA rose.
Keywords
Androgen receptor, steroidogenic enzyme, AKR3C1 SRD5A1, SRD5A2, SRD5A3
Figure 1
Figure 2
This is a list of supplementary files associated with this preprint. Click to download.
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 3
Posted 18 May, 2020
No comments provided
Editorial decision: Minor revision
On 24 Apr, 2020
Editor assigned
On 09 Feb, 2020
Submission checks complete
On 08 Feb, 2020
Editor invited
On 08 Feb, 2020
No comments provided
Editorial decision: Major revision
On 08 Jan, 2020
Review #2 received
Received 23 Dec, 2019
Reviewer #2 agreed
On 03 Dec, 2019
Review #1 received
Received 27 Aug, 2019
Reviewers invited
Invitations sent on 22 Aug, 2019
Reviewer #1 agreed
On 22 Aug, 2019
Editor assigned
On 02 Aug, 2019
Editor invited
On 19 Jul, 2019
Submission checks complete
On 18 Jul, 2019
First submitted
On 17 Jul, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Urology & Nephrology
Learn more about our company.
This preprint is under consideration at BMC Urology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Early upregulation of AR and steroidogenesis enzyme expression after 3 months of androgen-deprivation therapy.
Agus Rizal A.H. Hamid
Department of Urology, Cipto Mangunkusumo National Referral Hospital-University of Indonesia
Corresponding Author
ORCiD: https://orcid.org/0000-0002-7538-2811
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 3
Posted 18 May, 2020
No comments provided
Editorial decision: Minor revision
On 24 Apr, 2020
Editor assigned
On 09 Feb, 2020
Submission checks complete
On 08 Feb, 2020
Editor invited
On 08 Feb, 2020
No comments provided
Editorial decision: Major revision
On 08 Jan, 2020
Review #2 received
Received 23 Dec, 2019
Reviewer #2 agreed
On 03 Dec, 2019
Review #1 received
Received 27 Aug, 2019
Reviewers invited
Invitations sent on 22 Aug, 2019
Reviewer #1 agreed
On 22 Aug, 2019
Editor assigned
On 02 Aug, 2019
Editor invited
On 19 Jul, 2019
Submission checks complete
On 18 Jul, 2019
First submitted
On 17 Jul, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Urology & Nephrology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at BMC Urology.
Background: Androgen deprivation therapy (ADT) is a standard treatment for advanced prostate cancer (PCa). However, PCa recurrence and progression rates during ADT are high. Until now, there has been no evidence regarding when progression begins. This study evaluated the gene expression of intraprostatic androgen receptor (AR) and steroidogenic enzymes in the early stages of ADT.
Methods: Prostate tissue samples were taken from PCa patients with urinary retention who received ADT (ADT-PCa; n=10) and were further subgrouped into ADT ≤12 months (n=4) and ADT >12 months (n=6). The ADT-PCa tissues were then compared with BPH (n=12) and primary (no treatment) PCa tissues (n=16). mRNA for gene expression analysis of AR and steroidogenic enzymes was extracted from formalin-fixed paraffin embedded (FFPE) tissues and analyzed by real-time PCR. Protein expression was evaluated by immunohistochemistry with specific antibodies.
Results: AR gene expression was higher in the ADT-PCa group than in the BPH or primary PCa group. Both the ADT ≤12 and > 12 months subgroups had significantly higher relative gene expression levels of AR (p<0.01 and 0.03, respectively) than the primary PCa group. In the ADT-PCa group, AR protein expression showed an increasing trend in the ADT ≤12 months subgroup and was significantly elevated in the ADT >12 months subgroup compared with the PCa group (100%; p <0.01). Half (50%) of the patients in the ADT ≤12 months subgroup were found to have upregulation of AR, and one showed upregulation beginning at 3 months of ADT. A trend toward elevated relative gene expression of SRD5A3 was also apparent in the ADT groups.
Conclusion: AR and steroidogenic enzymes are upregulated in ADT-PCa patients as early as 3 months, without PSA elevation. Steroidogenic enzymes, particularly SRD5A3, were also upregulated before PSA rose.
Figure 1
Figure 2