PBX3 is a putative biomarker of aggressive prostate cancer.
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.
Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
Håkon
H
Ramberg
Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
Helene Hartvedt
HH
Grytli
Department of Informatics, University of Oslo, Oslo, Norway.
Ståle
S
Nygård
Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
Wanzhong
W
Wang
Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
Olov
O
Ögren
Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.|Center for Cancer Biomedicine, Medical Faculty, University of Oslo, Oslo, Norway.
Sen
S
Zhao
Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.|Center for Cancer Biomedicine, Medical Faculty, University of Oslo, Oslo, Norway.
Marthe
M
Løvf
Department of Pathology, Division of Diagnostics and Intervention, Oslo University Hospital, Oslo, Norway.
Betina
B
Katz
Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.|Center for Cancer Biomedicine, Medical Faculty, University of Oslo, Oslo, Norway.
Rolf I
RI
Skotheim
Department of Urology, Skåne University Hospital, Malmö, Sweden.|Department of Clinical Sciences Malmö, Division of Urological Cancers, Lund University, Lund, Sweden.
Anders
A
Bjartell
Department of Urology, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Lars Magne
LM
Eri
Department of Urology, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Viktor
V
Berge
Department of Pathology, Division of Diagnostics and Intervention, Oslo University Hospital, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Aud
A
Svindland
Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Kristin Austlid
KA
Taskén
D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism; D018450:Disease Progression; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D064129:Prostatic Neoplasms, Castration-Resistant / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D011518:Proto-Oncogene Proteins / Q000378:metabolism*
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins; C083400:PBX1 protein, human; C090466:proto-oncogene protein Pbx3
Biomarker; PBX; mortality; prostate cancer