Immunohistochemical staining of ERG and SOX9 as potential biomarkers of docetaxel response in patients with metastatic castration-resistant prostate cancer

Oncotarget. 2016 Dec 13;7(50):83735-83743. doi: 10.18632/oncotarget.13407.

Abstract

We aimed to evaluate ERG and SOX9 as potential biomarkers of docetaxel response in metastatic castration-resistant prostate cancer (mCRPC) patients. Seventy-one mCRPC patients were evaluated. Tissue microarrays were constructed and immunohistochemistry was performed. Treatment response was assessed by prostate specific antigen (PSA) response rate, PSA progression-free survival (PSA-PFS), clinical/radiologic PFS (C/R-PFS) and overall survival (OS). ERG and SOX9 were found in 13 (18.3%) and 62 (87.3%) patients, respectively. ERG-positive had lower PSA response rates than negative (15.4% vs 62.1%, p = 0.004), and SOX9 showed a same trend (46.8% vs 100.0%, p = 0.003). ERG positivity correlated with a lower PSA-PFS (3.2 mos vs 7.4 mos, p < 0.001), C/R-PFS (3.8 mos vs 9.0 mos, p < 0.001) and OS (10.8 mos vs 21.4 mos, p < 0.001). SOX9 positivity also showed a lower PSA-PFS, C/R-PFS and OS (p =0.006, p =0.012 and p =0.023, respectively). On multivariate analysis, ERG positivity was a significant risk factor for a lower PSA-PFS, C/R-PFS and OS (p < 0.001, p < 0.001 and p =0.001, respectively). SOX9 expression was also a risk factor for a lower PSA-PFS, C/R-PFS and OS (p = 0.018, p = 0.025 and p =0.047, respectively). These findings indicate that ERG and SOX9 is potential biomarkers for prediction to docetaxel treatment in mCRPC patients.

Keywords: ERG; SOX9; biomarker; docetaxel; prostate cancer.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / analysis*
  • Biopsy
  • Disease Progression
  • Disease-Free Survival
  • Docetaxel
  • Humans
  • Immunohistochemistry*
  • Kallikreins / blood
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms, Castration-Resistant / chemistry*
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / mortality
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Retrospective Studies
  • Risk Factors
  • SOX9 Transcription Factor / analysis*
  • Taxoids / adverse effects
  • Taxoids / therapeutic use*
  • Time Factors
  • Tissue Array Analysis
  • Transcriptional Regulator ERG / analysis
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • ERG protein, human
  • SOX9 Transcription Factor
  • SOX9 protein, human
  • Taxoids
  • Transcriptional Regulator ERG
  • Docetaxel
  • KLK3 protein, human
  • Kallikreins
  • Prostate-Specific Antigen