Doublecortin Expression in Prostate Adenocarcinoma and Neuroendocrine Tumors

Int J Radiat Oncol Biol Phys. 2020 Nov 15;108(4):936-940. doi: 10.1016/j.ijrobp.2020.06.024. Epub 2020 Jun 22.

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.

MeSH terms

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

Substances

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