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Role of serum response factor expression in prostate cancer biochemical recurrence

Prencipe, Maria ; Fabre, Aurelie ; Murphy, Thomas Brendan ; Vargyas, Eszter ; O'Neill, Amanda ; Bjartell, Anders LU ; Tasken, Kristin Austlid ; Grytli, Helene H ; Svindland, Aud and Berge, Viktor , et al. (2018) In The Prostate 78(10). p.724-730
Abstract

BACKGROUND: Up to a third of prostate cancer patients fail curative treatment strategies such as surgery and radiation therapy in the form of biochemical recurrence (BCR) which can be predictive of poor outcome. Recent clinical trials have shown that men experiencing BCR might benefit from earlier intervention post-radical prostatectomy (RP). Therefore, there is an urgent need to identify earlier prognostic biomarkers which will guide clinicians in making accurate diagnosis and timely decisions on the next appropriate treatment. The objective of this study was to evaluate Serum Response Factor (SRF) protein expression following RP and to investigate its association with BCR.

MATERIALS AND METHODS: SRF nuclear expression was... (More)

BACKGROUND: Up to a third of prostate cancer patients fail curative treatment strategies such as surgery and radiation therapy in the form of biochemical recurrence (BCR) which can be predictive of poor outcome. Recent clinical trials have shown that men experiencing BCR might benefit from earlier intervention post-radical prostatectomy (RP). Therefore, there is an urgent need to identify earlier prognostic biomarkers which will guide clinicians in making accurate diagnosis and timely decisions on the next appropriate treatment. The objective of this study was to evaluate Serum Response Factor (SRF) protein expression following RP and to investigate its association with BCR.

MATERIALS AND METHODS: SRF nuclear expression was evaluated by immunohistochemistry (IHC) in TMAs across three international radical prostatectomy cohorts for a total of 615 patients. Log-rank test and Kaplan-Meier analyses were used for BCR comparisons. Stepwise backwards elimination proportional hazard regression analysis was used to explore the significance of SRF in predicting BCR in the context of other clinical pathological variables. Area under the curve (AUC) values were generated by simulating repeated random sub-samples.

RESULTS: Analysis of the immunohistochemical staining of benign versus cancer cores showed higher expression of nuclear SRF protein expression in cancer cores compared with benign for all the three TMAs analysed (P < 0.001, n = 615). Kaplan-Meier curves of the three TMAs combined showed that patients with higher SRF nuclear expression had a shorter time to BCR compared with patients with lower SRF expression (P < 0.001, n = 215). Together with pathological T stage T3, SRF was identified as a predictor of BCR using stepwise backwards elimination proportional hazard regression analysis (P = 0.0521). Moreover ROC curves and AUC values showed that SRF was better than T stage in predicting BCR at year 3 and 5 following radical prostatectomy, the combination of SRF and T stage had a higher AUC value than the two taken separately.

CONCLUSIONS: SRF assessment by IHC following RP could be useful in guiding clinicians to better identify patients for appropriate follow-up and timely treatment.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Aged, Humans, Immunochemistry, Male, Middle Aged, Neoplasm Recurrence, Local/blood, Prostate/metabolism, Prostatic Neoplasms/blood, Serum Response Factor/biosynthesis, Survival Analysis
in
The Prostate
volume
78
issue
10
pages
7 pages
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:85044731627
  • pmid:29608018
ISSN
0270-4137
DOI
10.1002/pros.23516
language
English
LU publication?
yes
additional info
© 2018 Wiley Periodicals, Inc.
id
7305d49e-71a3-4878-82e6-3d47212bba42
date added to LUP
2019-06-26 10:28:30
date last changed
2024-04-16 13:49:39
@article{7305d49e-71a3-4878-82e6-3d47212bba42,
  abstract     = {{<p>BACKGROUND: Up to a third of prostate cancer patients fail curative treatment strategies such as surgery and radiation therapy in the form of biochemical recurrence (BCR) which can be predictive of poor outcome. Recent clinical trials have shown that men experiencing BCR might benefit from earlier intervention post-radical prostatectomy (RP). Therefore, there is an urgent need to identify earlier prognostic biomarkers which will guide clinicians in making accurate diagnosis and timely decisions on the next appropriate treatment. The objective of this study was to evaluate Serum Response Factor (SRF) protein expression following RP and to investigate its association with BCR.</p><p>MATERIALS AND METHODS: SRF nuclear expression was evaluated by immunohistochemistry (IHC) in TMAs across three international radical prostatectomy cohorts for a total of 615 patients. Log-rank test and Kaplan-Meier analyses were used for BCR comparisons. Stepwise backwards elimination proportional hazard regression analysis was used to explore the significance of SRF in predicting BCR in the context of other clinical pathological variables. Area under the curve (AUC) values were generated by simulating repeated random sub-samples.</p><p>RESULTS: Analysis of the immunohistochemical staining of benign versus cancer cores showed higher expression of nuclear SRF protein expression in cancer cores compared with benign for all the three TMAs analysed (P &lt; 0.001, n = 615). Kaplan-Meier curves of the three TMAs combined showed that patients with higher SRF nuclear expression had a shorter time to BCR compared with patients with lower SRF expression (P &lt; 0.001, n = 215). Together with pathological T stage T3, SRF was identified as a predictor of BCR using stepwise backwards elimination proportional hazard regression analysis (P = 0.0521). Moreover ROC curves and AUC values showed that SRF was better than T stage in predicting BCR at year 3 and 5 following radical prostatectomy, the combination of SRF and T stage had a higher AUC value than the two taken separately.</p><p>CONCLUSIONS: SRF assessment by IHC following RP could be useful in guiding clinicians to better identify patients for appropriate follow-up and timely treatment.</p>}},
  author       = {{Prencipe, Maria and Fabre, Aurelie and Murphy, Thomas Brendan and Vargyas, Eszter and O'Neill, Amanda and Bjartell, Anders and Tasken, Kristin Austlid and Grytli, Helene H and Svindland, Aud and Berge, Viktor and Eri, Lars M and Gallagher, William and Watson, R William}},
  issn         = {{0270-4137}},
  keywords     = {{Aged; Humans; Immunochemistry; Male; Middle Aged; Neoplasm Recurrence, Local/blood; Prostate/metabolism; Prostatic Neoplasms/blood; Serum Response Factor/biosynthesis; Survival Analysis}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{724--730}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{The Prostate}},
  title        = {{Role of serum response factor expression in prostate cancer biochemical recurrence}},
  url          = {{http://dx.doi.org/10.1002/pros.23516}},
  doi          = {{10.1002/pros.23516}},
  volume       = {{78}},
  year         = {{2018}},
}