Thrombospondin 1 and cathepsin D improve prostate cancer diagnosis by avoiding potentially unnecessary prostate biopsies

BJU Int. 2019 May;123(5):826-833. doi: 10.1111/bju.14540. Epub 2018 Oct 11.


Objectives: To investigate and further validate if two novel cancer-related glycoproteins, discovered by a genetic-guided proteomics approach, can distinguish benign disease from prostate cancer (PCa) in men with enlarged prostates.

Patients and methods: A retrospective study was performed that included men with a total prostate-specific antigen (PSA) concentration of 2.0-10 ng/mL, negative digital rectal examination and enlarged prostate (volume ≥35 mL). Serum samples were collected between 2011 and 2016 at a single centre from 474 men before they underwent prostate biopsy. Serum concentrations of thrombospondin 1 (THBS1) and cathepsin D (CTSD) glycoproteins were combined with the percentage of free PSA to total PSA ratio (%fPSA) to predict any or significant cancer at biopsy.

Results: The multivariable logistic regression model including THBS1, CTSD and %fPSA discriminated among biopsy-positive and biopsy-negative patients in the validation set with an area under the curve (AUC) of 0.86 (P < 0.001, 95% confidence interval (CI) 0.82-0.91), while %fPSA alone showed an AUC of 0.64 (P < 0.001, 95% CI 0.57-0.71). At 90% sensitivity for PCa, the specificity of the model was 62%, while %fPSA had a specificity of 23%. For high grade (Gleason score ≥ 7 in prostatectomy specimen) PCa, the specificity was 48% at 90% sensitivity, with an AUC of 0.83, (P < 0.001, 95% CI 0.77 to 0.88). Limitations of the study include the retrospective set-up and single-centre cohort.

Conclusions: A model combining two cancer-related glycoproteins (THBS1 and CTSD) and %fPSA can improve PCa diagnosis and may reduce the number of unnecessary prostate biopsies because of its improved specificity for PCa when compared to %fPSA alone.

Keywords: #ProstateCancer; biomarkers; cathepsin D; prostate-specific antigen; thrombospondin 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Area Under Curve
  • Biopsy*
  • Cathepsin D / blood*
  • Early Detection of Cancer* / methods
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prostate / pathology*
  • Prostate-Specific Antigen / blood*
  • Prostatic Neoplasms / blood*
  • Prostatic Neoplasms / pathology
  • Retrospective Studies
  • Thrombospondin 1 / blood*
  • Unnecessary Procedures*


  • Thrombospondin 1
  • Prostate-Specific Antigen
  • Cathepsin D