Somatic HOXB13 Expression Correlates with Metastatic Progression in Men with Localized Prostate Cancer Following Radical Prostatectomy.

Abstract

BACKGROUND:

Homeobox B13 (HOXB13) expression regulates normal prostate development and mutations are associated with prostate cancer (PCa) formation.

OBJECTIVE:

To assess the role of HOXB13 mRNA expression in PCa progression following radical prostatectomy.

DESIGN, SETTING, AND PARTICIPANTS:

Genome-wide expression profiles were queried from two retrospective prostatectomy cohorts with follow-up data (Mayo Clinic, n=780; Johns Hopkins Medical Institute [JHMI], n=355), and a prospective genomic registry (n=5239).

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

Multivariable Cox regressions were used to analyze metastasis-free survival (MFS).

RESULTS AND LIMITATIONS:

HOXB13 expression in primary PCa increased with increasing tumor grade and with high metastatic potential based on a genomic signature. The highest quartile of HOXB13 expression was associated with worse MFS compared with the lowest quartile (Mayo Clinic: adjusted hazard ratio [AHR] 1.46, 95% confidence interval [CI] 1.03-2.06, and JHMI: AHR 1.80, 95% CI 1.02-3.19). The combinations of high HOXB13 expression and low expression of its binding partner, MEIS1 (AHR 2.03, 95% CI 1.54-2.66) or MEIS2 (AHR 1.73, 95% CI 1.33-2.26), portended worse MFS. Additionally, high HOXB13 expression in combination with low MEIS1/2 expression correlated with high expression of androgen receptor-mediated genes. The retrospective nature of this study subjects the findings to a bias due to unmeasured variables.

CONCLUSIONS:

Primary PCa tumors with increased HOXB13 expression have an increased propensity for metastases following prostatectomy, particularly in the setting of low MEIS1/2 expression. High androgen receptor output may account for worse outcomes for these tumors and suggests heightened sensitivity to androgen suppression.

PATIENT SUMMARY:

Using genomic data from a large number of prostate cancer (PCa) tumors, we found that increased expression of homeobox B13 (HOXB13), a gene related to normal prostate development, was associated with worse outcomes following surgery for PCa. A biomarker signature suggests that these tumors would be more susceptible to androgen suppression, a common treatment for PCa. Take Home  Messagece:: In multiple large cohorts, prostate cancer tumors with high homeobox B13 (HOXB13) expression and low expression of its binding partner MEIS1/2 were enriched with high androgen receptor output and had an increased propensity for metastases following surgery.

• Authors: Adam B Weiner, Farzana A Faisal, Elai Davicioni, R Jeffrey Karnes, Donald J Vander Griend, Tamara L Lotan, Edward M Schaeffer
• Journal: European urology oncology (Eur Urol Oncol) Vol. 4 Issue 6 Pg. 955-962 (12 2021) ISSN: 2588-9311 [Electronic] Netherlands
• PMID: 32540218 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Chemical References

• HOXB13 protein, human
• Homeodomain Proteins

Topics

• Genes, Homeobox
• Homeodomain Proteins (genetics)
• Humans
• Male
• Prospective Studies
• Prostate
• Prostatectomy
• Prostatic Neoplasms (genetics, surgery)
• Retrospective Studies