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 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.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Ramberg H,Grytli HH,Nygård S,Wang W,Ögren O,Zhao S,Løvf M,Katz B,Skotheim RI,Bjartell A,Eri LM,Berge V,Svindland A,Taskén KAdoi
10.1002/ijc.30220subject
Has Abstractpub_date
2016-10-15 00:00:00pages
1810-20issue
8eissn
0020-7136issn
1097-0215journal_volume
139pub_type
杂志文章abstract::High BMI is a well-known risk factor for postmenopausal breast cancer. There have been some reports of excess risk in association with weight gain and WHR, but little is known about the influence of body fatness per se. Using data from the Malmö Diet and Cancer Study, a prospective cohort study, 12,159 postmenopausal ...
journal_title:International journal of cancer
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