title: BMI1, stem cell factor acting as novel serum-biomarker for Caucasian and African-American prostate cancer.
abstract: BACKGROUND
  Lack of reliable predictive biomarkers is a stumbling block in the management of prostate cancer (CaP). Prostate-specific antigen (PSA) widely used in clinics has several caveats as a CaP biomarker. African-American CaP patients have poor prognosis than Caucasians, and notably the serum-PSA does not perform well in this group. Further, some men with low serum-PSA remain unnoticed for CaP until they develop disease. Thus, there is a need to identify a reliable diagnostic and predictive biomarker of CaP. Here, we show that BMI1 stem-cell protein is secretory and could be explored for biomarker use in CaP patients.
  
  
  RESULTS
  Semi-quantitative analysis of BMI1 was performed in prostatic tissues of TRAMP (autochthonous transgenic mouse model), human CaP patients, and in cell-based models representing normal and different CaP phenotypes in African-American and Caucasian men, by employing immunohistochemistry, immunoblotting and Slot-blotting. Quantitative analysis of BMI1 and PSA were performed in blood and culture-media of siRNA-transfected and non-transfected cells by employing ELISA. BMI1 protein is (i) secreted by CaP cells, (ii) increased in the apical region of epithelial cells and stromal region in prostatic tumors, and (iii) detected in human blood. BMI1 is detectable in blood of CaP patients in an order of increasing tumor stage, exhibit a positive correlation with serum-PSA and importantly is detectable in patients which exhibit low serum-PSA. The clinical significance of BMI1 as a biomarker could be ascertained from observation that CaP cells secrete this protein in higher levels than cells representative of benign prostatic hyperplasia (BPH).
  
  
  CONCLUSIONS
  BMI1 could be developed as a dual bio-marker (serum and biopsy) for the diagnosis and prognosis of CaP in Caucasian and African-American men. Though compelling these data warrant further investigation in a cohort of African-American patients.
authors: Molecular Chemoprevention and Therapeutics, The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors: Hifzur Rahman
authors: HR
authors: Siddique
authors: Aijaz
authors: A
authors: Parray
authors: Weixiong
authors: W
authors: Zhong
authors: R Jeffery
authors: RJ
authors: Karnes
authors: Eric J
authors: EJ
authors: Bergstralh
authors: Shahriar
authors: S
authors: Koochekpour
authors: Johng S
authors: JS
authors: Rhim
authors: Badrinath R
authors: BR
authors: Konety
authors: Mohammad
authors: M
authors: Saleem
mesh_terms: D001741:Black or African American; D000818:Animals; D001706:Biopsy; D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D063150:Polycomb Repressive Complex 1 / Q000032:analysis / Q000097:blood*; D011467:Prostate / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000032:analysis; D044465:White People
chemical_list: C069077:BMI1 protein, human; C489421:Bmi1 protein, mouse; D011518:Proto-Oncogene Proteins; D063150:Polycomb Repressive Complex 1; D017430:Prostate-Specific Antigen