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PBX3 is a putative biomarker of aggressive prostate cancer

Ramberg, Håkon; Grytli, Helene Hartvedt; Nygård, Ståle; Wang, Wanzhong; Ögren, Olov; Zhao, Sen; Løvf, Marthe; Katz, Betina; Skotheim, Rolf I. and Bjartell, Anders LU , et al. (2016) In International Journal of Cancer 139(8). p.1810-1820
Abstract

There is a great need to identify new and better prognostic and predictive biomarkers to stratify prostate cancer patients for optimal treatment. The aims of this study were to characterize the expression profile of pre-B cell leukemia homeobox (PBX) transcription factors in prostate cancer with an emphasis on investigating whether PBX3 harbours any prognostic value. The expression profile of PBX3 and PBX1 in prostate tissue was determined by immunohistochemical and immunoblot analysis. Furthermore, the expression of PBX3 transcript variants was analyzed by RT-PCR, NanoString Technologies®, and by analyzing RNA sequence data. The potential of PBX3 to predict prognosis, either at mRNA or protein level, was studied in four independent... (More)

There is a great need to identify new and better prognostic and predictive biomarkers to stratify prostate cancer patients for optimal treatment. The aims of this study were to characterize the expression profile of pre-B cell leukemia homeobox (PBX) transcription factors in prostate cancer with an emphasis on investigating whether PBX3 harbours any prognostic value. The expression profile of PBX3 and PBX1 in prostate tissue was determined by immunohistochemical and immunoblot analysis. Furthermore, the expression of PBX3 transcript variants was analyzed by RT-PCR, NanoString Technologies®, and by analyzing RNA sequence data. The potential of PBX3 to predict prognosis, either at mRNA or protein level, was studied in four independent cohorts. PBX3 was mainly expressed in the nucleus of normal prostate basal cells, while it showed cytosolic expression in prostatic intraepithelial neoplasia and cancer cells. We detected four PBX3 transcript variants in prostate tissue. Competing risk regression analysis revealed that high PBX3 expression was associated with slower progression to castration resistant prostate cancer (sub-hazard ratio (SHR) 0.18, 95% CI: 0.081–0.42, p values < 0.001). PBX3 expression had a high predictive accuracy (area under the curve (AUC) = 0.82) when combined with Gleason score and age. Patients undergoing radical prostatectomy, with high levels of PBX3 mRNA, had improved prostate cancer specific survival compared to patients expressing low levels (SHR 0.21, 95% CI: 0.46–0.93, p values < 0.001, and AUC = 0.75). Our findings strongly indicate that PBX3 has potential as a biomarker, both as part of a larger gene panel and as an immunohistochemical marker, for aggressive prostate cancer.

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Contribution to journal
publication status
published
subject
keywords
Biomarker, mortality, PBX, prostate cancer
in
International Journal of Cancer
volume
139
issue
8
pages
11 pages
publisher
John Wiley & Sons
external identifiers
  • Scopus:84981215858
  • WOS:000383284500015
ISSN
0020-7136
DOI
10.1002/ijc.30220
language
English
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yes
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dd77c4c4-ecf6-456a-acb8-ba90b5846e4c
date added to LUP
2016-10-14 10:32:26
date last changed
2017-02-05 04:53:57
@article{dd77c4c4-ecf6-456a-acb8-ba90b5846e4c,
  abstract     = {<p>There is a great need to identify new and better prognostic and predictive biomarkers to stratify prostate cancer patients for optimal treatment. The aims of this study were to characterize the expression profile of pre-B cell leukemia homeobox (PBX) transcription factors in prostate cancer with an emphasis on investigating whether PBX3 harbours any prognostic value. The expression profile of PBX3 and PBX1 in prostate tissue was determined by immunohistochemical and immunoblot analysis. Furthermore, the expression of PBX3 transcript variants was analyzed by RT-PCR, NanoString Technologies®, and by analyzing RNA sequence data. The potential of PBX3 to predict prognosis, either at mRNA or protein level, was studied in four independent cohorts. PBX3 was mainly expressed in the nucleus of normal prostate basal cells, while it showed cytosolic expression in prostatic intraepithelial neoplasia and cancer cells. We detected four PBX3 transcript variants in prostate tissue. Competing risk regression analysis revealed that high PBX3 expression was associated with slower progression to castration resistant prostate cancer (sub-hazard ratio (SHR) 0.18, 95% CI: 0.081–0.42, p values &lt; 0.001). PBX3 expression had a high predictive accuracy (area under the curve (AUC) = 0.82) when combined with Gleason score and age. Patients undergoing radical prostatectomy, with high levels of PBX3 mRNA, had improved prostate cancer specific survival compared to patients expressing low levels (SHR 0.21, 95% CI: 0.46–0.93, p values &lt; 0.001, and AUC = 0.75). Our findings strongly indicate that PBX3 has potential as a biomarker, both as part of a larger gene panel and as an immunohistochemical marker, for aggressive prostate cancer.</p>},
  author       = {Ramberg, Håkon and Grytli, Helene Hartvedt and Nygård, Ståle and Wang, Wanzhong and Ögren, Olov and Zhao, Sen and Løvf, Marthe and Katz, Betina and Skotheim, Rolf I. and Bjartell, Anders and Eri, Lars Magne and Berge, Viktor and Svindland, Aud and Taskén, Kristin Austlid},
  issn         = {0020-7136},
  keyword      = {Biomarker,mortality,PBX,prostate cancer},
  language     = {eng},
  month        = {10},
  number       = {8},
  pages        = {1810--1820},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {PBX3 is a putative biomarker of aggressive prostate cancer},
  url          = {http://dx.doi.org/10.1002/ijc.30220},
  volume       = {139},
  year         = {2016},
}