BMI1, Stem Cell Factor Acting as Novel Serum-biomarker for Caucasian and African-American Prostate Cancer

Hifzur Rahman Siddique, Aijaz Parray, Weixiong Zhong, Robert Jeffrey Karnes, Eric J. Bergstralh, Shahriar Koochekpour, Johng S. Rhim, Badrinath R. Konety, Mohammad Saleem

Research output: Contribution to journalArticle

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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. Methodology/Principal Findings: 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/Significance: 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.

Original languageEnglish (US)
Article numbere52993
JournalPLoS One
Volume8
Issue number1
DOIs
StatePublished - Jan 7 2013

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prostate-specific antigen
stem cell factor
Stem Cell Factor
prostatic neoplasms
Biomarkers
African Americans
Prostate-Specific Antigen
blood serum
biomarkers
Prostatic Neoplasms
Serum
Blood
prognosis
cells
quantitative analysis
Tumors
blood
Proteins
proteins
Biopsy

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Siddique, H. R., Parray, A., Zhong, W., Karnes, R. J., Bergstralh, E. J., Koochekpour, S., ... Saleem, M. (2013). BMI1, Stem Cell Factor Acting as Novel Serum-biomarker for Caucasian and African-American Prostate Cancer. PLoS One, 8(1), [e52993]. https://doi.org/10.1371/journal.pone.0052993

BMI1, Stem Cell Factor Acting as Novel Serum-biomarker for Caucasian and African-American Prostate Cancer. / Siddique, Hifzur Rahman; Parray, Aijaz; Zhong, Weixiong; Karnes, Robert Jeffrey; Bergstralh, Eric J.; Koochekpour, Shahriar; Rhim, Johng S.; Konety, Badrinath R.; Saleem, Mohammad.

In: PLoS One, Vol. 8, No. 1, e52993, 07.01.2013.

Research output: Contribution to journalArticle

Siddique, HR, Parray, A, Zhong, W, Karnes, RJ, Bergstralh, EJ, Koochekpour, S, Rhim, JS, Konety, BR & Saleem, M 2013, 'BMI1, Stem Cell Factor Acting as Novel Serum-biomarker for Caucasian and African-American Prostate Cancer', PLoS One, vol. 8, no. 1, e52993. https://doi.org/10.1371/journal.pone.0052993
Siddique, Hifzur Rahman ; Parray, Aijaz ; Zhong, Weixiong ; Karnes, Robert Jeffrey ; Bergstralh, Eric J. ; Koochekpour, Shahriar ; Rhim, Johng S. ; Konety, Badrinath R. ; Saleem, Mohammad. / BMI1, Stem Cell Factor Acting as Novel Serum-biomarker for Caucasian and African-American Prostate Cancer. In: PLoS One. 2013 ; Vol. 8, No. 1.
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