Taxane-based Chemotherapy Induced Androgen Receptor Splice Variant 7 in Patients with Castration-Resistant Prostate Cancer: A Tissue-based Analysis

Sci Rep. 2019 Nov 14;9(1):16794. doi: 10.1038/s41598-019-53280-5.

Abstract

In total, 95 prostate cancer (Pca) patients who underwent transurethral resection of the prostate from 2000 to 2013 were assigned to four groups: Group 1, hormone-naïve and T1a or T1b Pca (n = 17); Group 2, hormone-sensitive and metastatic Pca (n = 33); Group 3, chemo-naïve castration-resistant Pca (CRPC), (n = 18); and Group 4, CRPC with chemotherapy (n = 27). Full-length androgen receptor (ARfl) transcript levels significantly increased from Group 1 through to Group 3 (p = 0.045), but decreased from Group 3 through to Group 4. AR splice variant 7 (ARV7) and glucocorticoid receptor (GR) transcript levels significantly increased from Group 1 through to Group 4 (p = 0.002 and 0.049, respectively). Kaplan-Meier curve revealed that the high transcript level of these three receptors resulted in significantly poorer cancer-specific survival (CSS) than that by low transcript level, although Cox regression analysis revealed that the ARV7 level alone was an independent prognostic factor for CSS in CRPC patients (high vs. low: hazard ratio, 1.897; 95% confidence interval, 1.102-3.625; p = 0.042). In conclusion, ARV7 and GR transcript levels significantly increase as Pca progresses to CRPC.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alternative Splicing*
  • Bridged-Ring Compounds / administration & dosage*
  • Bridged-Ring Compounds / pharmacology
  • Cell Line, Tumor
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Male
  • Organ Specificity
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / genetics
  • Receptors, Androgen / genetics*
  • Receptors, Glucocorticoid / genetics
  • Regression Analysis
  • Survival Analysis
  • Taxoids / administration & dosage*
  • Taxoids / pharmacology
  • Treatment Outcome

Substances

  • AR protein, human
  • Bridged-Ring Compounds
  • Receptors, Androgen
  • Receptors, Glucocorticoid
  • Taxoids
  • taxane