Doublecortin Expression in Prostate Adenocarcinoma and Neuroendocrine Tumors.

Abstract

PURPOSE:

Recent work using prostate cancer mouse models implicated doublecortin (DCX)-expressing neural progenitor cells in prostate adenocarcinoma, reporting a strong association between DCX expression and histologic grade and clinical outcome. We sought to evaluate the relationship between DCX expression and these variables in human prostate cancer.

METHODS AND MATERIALS:

DCX expression was measured in transcriptome-wide microarray data from 18,501 patients with localized prostate cancer and 290 patients with metastatic castration-resistant prostate cancer (mCRPC) and compared across disease states, histologic grades, and clinical outcomes. Biochemical recurrence-free survival (BRFS), metastasis-free survival (MFS), and overall survival (OS) were analyzed using Cox proportional hazards.

RESULTS:

DCX expression was not significantly different among normal prostate (n = 29), primary prostate cancer (n = 131), and metastases (n = 19) and did not increase with grade in a large cohort of radical prostatectomy samples (n = 17,967). Those with DCX expression above and below the median did not have significant differences in BRFS (HR 1.15 [95% confidence interval, 0.88-1.49], P = .31), MFS (HR 1.2 [0.84-1.7], P = .3), or OS (HR 1.15 [0.7-1.84], P = .56). In a cohort with untreated prostate cancer, DCX expression was higher in neuroendocrine tumors (n = 10) compared with grade group 5 prostate adenocarcinoma (n = 110) (P = .007). Similarly, in 2 cohorts with mCRPC (n = 290), DCX expression was higher in lesions with neuroendocrine features compared with adenocarcinoma (P < .001).

CONCLUSIONS:

Contrary to recent data using mouse models, DCX expression did not differ by disease state or outcome and did not increase with grade in a large data set of patients with prostate adenocarcinoma. However, DCX expression appeared to correlate with neuroendocrine histology, a subgroup that can arise de novo or in the castrate-resistant setting. Further work is needed to define the role of DCX and its clinical significance in prostate cancer.

• Authors: Shervin Tabrizi, Mohammed Alshalalfa, Brandon A Mahal, Elai Davicioni, Yang Liu, Kent W Mouw, Felix Feng, Paul L Nguyen, Vinayak Muralidhar
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 108 Issue 4 Pg. 936-940 (11 15 2020) ISSN: 1879-355X [Electronic] United States
• PMID: 32585335 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• DCX protein, human
• Dcx protein, mouse
• Doublecortin Domain Proteins
• Doublecortin Protein
• Microtubule-Associated Proteins
• Neoplasm Proteins
• Neuropeptides

Topics

• Adenocarcinoma (metabolism, mortality, pathology)
• Confidence Intervals
• Doublecortin Domain Proteins
• Doublecortin Protein
• Humans
• Linear Models
• Male
• Microtubule-Associated Proteins (metabolism)
• Neoplasm Proteins (metabolism)
• Neuroendocrine Tumors (metabolism, mortality, pathology)
• Neuropeptides (metabolism)
• Prostate (metabolism)
• Prostatic Neoplasms (metabolism, mortality, pathology)
• Prostatic Neoplasms, Castration-Resistant (metabolism, mortality, pathology)
• Statistics, Nonparametric