161 Background: 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 disease progression and outcome. We sought to evaluate the relationship between DCX expression and these outcomes in human prostate cancer. Methods: 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). Pairwise comparisons were performed using the Mann–Whitney U test. Metastasis-free survival (MFS) and overall survival (OS) were analyzed using Cox-proportional hazards. Results: DCX expression was not significantly different between normal prostate (n=29), primary prostate cancer (n=131), or metastases (n=19) (p > 0.5), and did not differ across Gleason score in a large cohort of RP samples (n=17,967, p=0.21). The lack of difference persisted after adjusting for stromal contribution using a 141-gene stromal signature. Those with DCX expression above and below the median did not have significant differences in MFS (HR 1.2 [0.84-1.7], p=0.3) or OS (HR 1.15 [0.7-1.84], p =0.56). In a cohort of untreated prostate cancer, DCX expression was higher in neuroendocrine tumors (n=10) compared to Gleason 9-10 prostate adenocarcinoma (n=110) (p=0.007). Similarly, in two cohorts with mCRPC (n=290), DCX expression was higher in lesions with neuroendocrine features than adenocarcinoma (p<0.001). Consistently, in a patient-derived xenograft model subjected to host castration, DCX expression was initially low, but increased significantly once tumors underwent neuroendocrine differentiation and treatment escape. Conclusions: Contrary to recent data using mouse models, DCX expression did not differ by disease state, grade, or outcome in a dataset of human patients with prostate adenocarcinoma. However, DCX expression appeared to correlate with neuroendocrine prostate cancers, a subgroup that can arise de novo or in the castrate-resistant setting. Further work is needed to define the role of DCX expression and its prognostic significance in prostate cancer.
Mouse Models of Prostate Adenocarcinoma with the Capacity to Monitor Spontaneous Carcinogenesis by Bioluminescence or Fluorescence
