Low expression of the androgen-induced tumor suppressor gene PLZF and lethal prostate cancer Journal Article

   


Authors: Stopsack, K. H.; Gerke, T.; Tyekucheva, S.; Mazzu, Y. Z.; Lee, G. S. M.; Chakraborty, G.; Abida, W.; Mucci, L. A.; Kantoff, P. W.
Article Title: Low expression of the androgen-induced tumor suppressor gene PLZF and lethal prostate cancer
Abstract: Background: 4%–9% of prostate cancers harbor homozygous deletions of the androgen-induced tumor suppressor gene, promyelocytic leukemia zinc finger (PLZF, ZBTB16). PLZF loss induces an in vitro phenotype of castration resistance and enzalutamide resistance. The association of low expression of PLZF and clinical outcomes is unclear. Methods: We assessed PLZF mRNA expression in patients diagnosed with primary prostate cancer during prospective follow-up of the Health Professionals Follow-up Study (HPFS; n 1⁄4 254) and the Physicians' Health Study (PHS; n 1⁄4 150), as well as in The Cancer Genome Atlas (n 1⁄4 333). We measured PTEN status (using copy numbers and IHC) and transcriptional activation of the MAPK pathway. Patients from HPFS and PHS were followed for metastases and prostate cancer–specific mortality (median, 15.3 years; 113 lethal events). Results: PLZF mRNA expression was lower in tumors with PLZF deletions. There was a strong, positive association between intratumoral androgen receptor (AR) signaling and PLZF expression. PLZF expression was also lower in tumors with PTEN loss. Low PLZF expression was associated with higher MAPK signaling. Patients in the lowest quartile of PLZF expression compared with those in the highest quartile were more likely to develop lethal prostate cancer, independent of clinicopathologic features, Gleason score, and AR signaling (odds ratio, 3.17; 95% confidence interval, 1.32–7.60). Conclusions: Low expression of the tumor suppressor gene PLZF is associated with a worse prognosis in primary prostate cancer. Impact: Suppression of PLZF as a consequence of androgen deprivation may be undesirable. PLZF should be tested as a predictive marker for resistance to androgen deprivation therapy. © 2019 American Association for Cancer Research.
Keywords: immunohistochemistry; mitogen activated protein kinase; adult; controlled study; human tissue; aged; major clinical study; cancer patient; prospective study; metastasis; gene expression; transcription initiation; cancer mortality; prostate cancer; gleason score; tumor suppressor gene; messenger rna; prostatectomy; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; androgen receptor; transurethral resection; cancer prognosis; human; male; priority journal; article; zinc finger and btb domain containing protein 16
Journal Title: Cancer Epidemiology Biomarkers and Prevention
Volume: 28
Issue: 4
ISSN: 1055-9965
Publisher: American Association for Cancer Research  
Date Published: 2019-04-01
Start Page: 707
End Page: 714
Language: English
DOI: 10.1158/1055-9965.Epi-18-1014
PUBMED: 30602500
PROVIDER: scopus
PMCID: PMC6532645
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85063911176&doi=10.1158%2f1055-9965.EPI-18-1014&partnerID=40&md5=329ebefcb3a82672ed51c021761359fb
Notes: Article -- Export Date: 1 May 2019 -- Source: Scopus
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MSK Authors
  1. Goutam Chakraborty
    44 Chakraborty
  2. Wassim Abida
    143 Abida
  3. Ying Zhang Mazzu
    34 Mazzu
  4. Philip Wayne Kantoff
    190 Kantoff
  5. Konrad Hermann Stopsack
    66 Stopsack
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