Protein Kinase A RI-α Predicts for Prostate Cancer Outcome: Analysis of Radiation Therapy Oncology Group Trial 86-10

Li Yan Khor, Kyounghwa Bae, Tahseen Al-Saleem, Elizabeth H. Hammond, David Grignon, William T. Sause, Miljenko V. Pilepich, Paul P. Okunieff, Howard M. Sandler, Alan Pollack

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Purpose: The RI-α regulatory subunit of protein kinase A type 1 (PKA) is constitutively overexpressed in human cancer cell lines and is associated with active cell growth and neoplastic transformation. This report examined the association between PKA expression and the endpoints of biochemical failure (BF), local failure (LF), distant metastasis (DM), cause-specific mortality (CSM), and overall mortality in men treated with radiotherapy, with or without short-term androgen deprivation in Radiation Therapy Oncology Group trial 86-10. Methods and Materials: Pretreatment archival diagnostic tissue samples from 80 patients were stained for PKA by immunohistochemical methods from a parent cohort of 456 cases. PKA intensity was scored manually and by image analysis. The Cox proportional hazards model for overall mortality and Fine and Gray's regression models for CSM, DM, LF and BF were then applied to determine the relationship of PKA expression to the endpoints. Results: The pretreatment characteristics of the missing and determined PKA groups were not significantly different. On univariate analyses, a high PKA staining intensity was associated with BF (image analysis, continuous variable, p = 0.022), LF (image analysis, dichotomized variable, p = 0.011), CSM (manual analysis, p = 0.037; image analysis, continuous, p = 0.014), and DM (manual analysis, p = 0.029). On multivariate analyses, the relationships to BF (image analysis, continuous, p = 0.03), LF (image analysis, dichotomized, p = 0.002), and DM remained significant (manual analysis, p = 0.018). In terms of CSM, a trend toward an association was seen (manual analysis, p = 0.08; image analysis, continuous, p = 0.09). Conclusion: PKA overexpression was significantly related to patient outcome and is a potentially useful biomarker for identifying high-risk prostate cancer patients who might benefit from a PKA knockdown strategy.

Original languageEnglish
Pages (from-to)1309-1315
Number of pages7
JournalInternational Journal of Radiation Oncology Biology Physics
Volume71
Issue number5
DOIs
StatePublished - Aug 1 2008

Fingerprint

Cyclic AMP-Dependent Protein Kinase Type I
Radiation Oncology
Cyclic AMP-Dependent Protein Kinases
radiation therapy
Prostatic Neoplasms
Radiotherapy
image analysis
mortality
cancer
proteins
metastasis
Mortality
Neoplasm Metastasis
causes
pretreatment
Neoplastic Cell Transformation
deprivation
biomarkers
staining
Proportional Hazards Models

Keywords

  • Androgen deprivation
  • PKA RI-α
  • Protein kinase A RI-α
  • Radiotherapy

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

Protein Kinase A RI-α Predicts for Prostate Cancer Outcome : Analysis of Radiation Therapy Oncology Group Trial 86-10. / Khor, Li Yan; Bae, Kyounghwa; Al-Saleem, Tahseen; Hammond, Elizabeth H.; Grignon, David; Sause, William T.; Pilepich, Miljenko V.; Okunieff, Paul P.; Sandler, Howard M.; Pollack, Alan.

In: International Journal of Radiation Oncology Biology Physics, Vol. 71, No. 5, 01.08.2008, p. 1309-1315.

Research output: Contribution to journalArticle

Khor, Li Yan ; Bae, Kyounghwa ; Al-Saleem, Tahseen ; Hammond, Elizabeth H. ; Grignon, David ; Sause, William T. ; Pilepich, Miljenko V. ; Okunieff, Paul P. ; Sandler, Howard M. ; Pollack, Alan. / Protein Kinase A RI-α Predicts for Prostate Cancer Outcome : Analysis of Radiation Therapy Oncology Group Trial 86-10. In: International Journal of Radiation Oncology Biology Physics. 2008 ; Vol. 71, No. 5. pp. 1309-1315.
@article{245c2f2c48b9408ab769a6d4eacf00aa,
title = "Protein Kinase A RI-α Predicts for Prostate Cancer Outcome: Analysis of Radiation Therapy Oncology Group Trial 86-10",
abstract = "Purpose: The RI-α regulatory subunit of protein kinase A type 1 (PKA) is constitutively overexpressed in human cancer cell lines and is associated with active cell growth and neoplastic transformation. This report examined the association between PKA expression and the endpoints of biochemical failure (BF), local failure (LF), distant metastasis (DM), cause-specific mortality (CSM), and overall mortality in men treated with radiotherapy, with or without short-term androgen deprivation in Radiation Therapy Oncology Group trial 86-10. Methods and Materials: Pretreatment archival diagnostic tissue samples from 80 patients were stained for PKA by immunohistochemical methods from a parent cohort of 456 cases. PKA intensity was scored manually and by image analysis. The Cox proportional hazards model for overall mortality and Fine and Gray's regression models for CSM, DM, LF and BF were then applied to determine the relationship of PKA expression to the endpoints. Results: The pretreatment characteristics of the missing and determined PKA groups were not significantly different. On univariate analyses, a high PKA staining intensity was associated with BF (image analysis, continuous variable, p = 0.022), LF (image analysis, dichotomized variable, p = 0.011), CSM (manual analysis, p = 0.037; image analysis, continuous, p = 0.014), and DM (manual analysis, p = 0.029). On multivariate analyses, the relationships to BF (image analysis, continuous, p = 0.03), LF (image analysis, dichotomized, p = 0.002), and DM remained significant (manual analysis, p = 0.018). In terms of CSM, a trend toward an association was seen (manual analysis, p = 0.08; image analysis, continuous, p = 0.09). Conclusion: PKA overexpression was significantly related to patient outcome and is a potentially useful biomarker for identifying high-risk prostate cancer patients who might benefit from a PKA knockdown strategy.",
keywords = "Androgen deprivation, PKA RI-α, Protein kinase A RI-α, Radiotherapy",
author = "Khor, {Li Yan} and Kyounghwa Bae and Tahseen Al-Saleem and Hammond, {Elizabeth H.} and David Grignon and Sause, {William T.} and Pilepich, {Miljenko V.} and Okunieff, {Paul P.} and Sandler, {Howard M.} and Alan Pollack",
year = "2008",
month = "8",
day = "1",
doi = "10.1016/j.ijrobp.2007.12.010",
language = "English",
volume = "71",
pages = "1309--1315",
journal = "International Journal of Radiation Oncology Biology Physics",
issn = "0360-3016",
publisher = "Elsevier Inc.",
number = "5",

}

TY - JOUR

T1 - Protein Kinase A RI-α Predicts for Prostate Cancer Outcome

T2 - Analysis of Radiation Therapy Oncology Group Trial 86-10

AU - Khor, Li Yan

AU - Bae, Kyounghwa

AU - Al-Saleem, Tahseen

AU - Hammond, Elizabeth H.

AU - Grignon, David

AU - Sause, William T.

AU - Pilepich, Miljenko V.

AU - Okunieff, Paul P.

AU - Sandler, Howard M.

AU - Pollack, Alan

PY - 2008/8/1

Y1 - 2008/8/1

N2 - Purpose: The RI-α regulatory subunit of protein kinase A type 1 (PKA) is constitutively overexpressed in human cancer cell lines and is associated with active cell growth and neoplastic transformation. This report examined the association between PKA expression and the endpoints of biochemical failure (BF), local failure (LF), distant metastasis (DM), cause-specific mortality (CSM), and overall mortality in men treated with radiotherapy, with or without short-term androgen deprivation in Radiation Therapy Oncology Group trial 86-10. Methods and Materials: Pretreatment archival diagnostic tissue samples from 80 patients were stained for PKA by immunohistochemical methods from a parent cohort of 456 cases. PKA intensity was scored manually and by image analysis. The Cox proportional hazards model for overall mortality and Fine and Gray's regression models for CSM, DM, LF and BF were then applied to determine the relationship of PKA expression to the endpoints. Results: The pretreatment characteristics of the missing and determined PKA groups were not significantly different. On univariate analyses, a high PKA staining intensity was associated with BF (image analysis, continuous variable, p = 0.022), LF (image analysis, dichotomized variable, p = 0.011), CSM (manual analysis, p = 0.037; image analysis, continuous, p = 0.014), and DM (manual analysis, p = 0.029). On multivariate analyses, the relationships to BF (image analysis, continuous, p = 0.03), LF (image analysis, dichotomized, p = 0.002), and DM remained significant (manual analysis, p = 0.018). In terms of CSM, a trend toward an association was seen (manual analysis, p = 0.08; image analysis, continuous, p = 0.09). Conclusion: PKA overexpression was significantly related to patient outcome and is a potentially useful biomarker for identifying high-risk prostate cancer patients who might benefit from a PKA knockdown strategy.

AB - Purpose: The RI-α regulatory subunit of protein kinase A type 1 (PKA) is constitutively overexpressed in human cancer cell lines and is associated with active cell growth and neoplastic transformation. This report examined the association between PKA expression and the endpoints of biochemical failure (BF), local failure (LF), distant metastasis (DM), cause-specific mortality (CSM), and overall mortality in men treated with radiotherapy, with or without short-term androgen deprivation in Radiation Therapy Oncology Group trial 86-10. Methods and Materials: Pretreatment archival diagnostic tissue samples from 80 patients were stained for PKA by immunohistochemical methods from a parent cohort of 456 cases. PKA intensity was scored manually and by image analysis. The Cox proportional hazards model for overall mortality and Fine and Gray's regression models for CSM, DM, LF and BF were then applied to determine the relationship of PKA expression to the endpoints. Results: The pretreatment characteristics of the missing and determined PKA groups were not significantly different. On univariate analyses, a high PKA staining intensity was associated with BF (image analysis, continuous variable, p = 0.022), LF (image analysis, dichotomized variable, p = 0.011), CSM (manual analysis, p = 0.037; image analysis, continuous, p = 0.014), and DM (manual analysis, p = 0.029). On multivariate analyses, the relationships to BF (image analysis, continuous, p = 0.03), LF (image analysis, dichotomized, p = 0.002), and DM remained significant (manual analysis, p = 0.018). In terms of CSM, a trend toward an association was seen (manual analysis, p = 0.08; image analysis, continuous, p = 0.09). Conclusion: PKA overexpression was significantly related to patient outcome and is a potentially useful biomarker for identifying high-risk prostate cancer patients who might benefit from a PKA knockdown strategy.

KW - Androgen deprivation

KW - PKA RI-α

KW - Protein kinase A RI-α

KW - Radiotherapy

UR - http://www.scopus.com/inward/record.url?scp=47349100409&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=47349100409&partnerID=8YFLogxK

U2 - 10.1016/j.ijrobp.2007.12.010

DO - 10.1016/j.ijrobp.2007.12.010

M3 - Article

C2 - 18455330

AN - SCOPUS:47349100409

VL - 71

SP - 1309

EP - 1315

JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

SN - 0360-3016

IS - 5

ER -