Expression of urokinase-type plasminogen activator system in non-metastatic prostate cancer

Abstract

Purpose

To investigate the prognostic role of expression of urokinase-type plasminogen activator system members, such as urokinase-type activator (uPA), uPA-receptor (uPAR), and plasminogen activator inhibitor-1 (PAI-1), in patients treated with radical prostatectomy (RP) for prostate cancer (PCa).

Methods

Immunohistochemical staining for uPA system was performed on a tissue microarray of specimens from 3121 patients who underwent RP. Cox regression analyses were performed to investigate the association of overexpression of these markers alone or in combination with biochemical recurrence (BCR). Decision curve analysis was used to assess the clinical impact of these markers.

Results

uPA, uPAR, and PAI-1 were overexpressed in 1012 (32.4%), 1271 (40.7%), and 1311 (42%) patients, respectively. uPA overexpression was associated with all clinicopathologic characteristics of biologically aggressive PCa. On multivariable analysis, uPA, uPAR, and PAI-1 overexpression were all three associated with BCR (HR: 1.75, p < 0.01, HR: 1.22, p = 0.01 and HR: 1.20, p = 0.03, respectively). Moreover, the probability of BCR increased incrementally with increasing cumulative number of overexpressed markers. Decision curve analysis showed that addition of uPA, uPAR, and PAI-1 resulted in a net benefit compared to a base model comparing standard clinicopathologic features across the entire threshold probability range. In subgroup analyses, overexpression of all three markers remained associated with BCR in patients with favorable pathologic characteristics.

Conclusion

Overexpression of uPA, uPAR, and PAI-1 in PCa tissue were each associated with worse BCR. Additionally, overexpression of all three markers is informative even in patients with favorable pathologic characteristics potentially helping clinical decision-making regarding adjuvant therapy and/or intensified follow-up.

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SK: protocol/project development, data collection, data analysis, and manuscript writing/editing. DD: data collection and data analysis. TI: manuscript writing/editing. BF: data collection, data analysis, and manuscript writing/editing. FJ: data collection and manuscript writing/editing. MKP: data collection and manuscript writing/editing. MM: data collection and manuscript writing/editing. AB: manuscript writing/editing. MB: manuscript writing/editing. PC: manuscript writing/editing. PIK: data collection and manuscript writing/editing. DE: data collection and manuscript writing/editing. LMR: data collection and manuscript writing/editing. VS: manuscript writing/editing. SE: protocol/project development. MA: data collection, data analysis, and manuscript writing/editing. SFS: protocol/project development and manuscript writing/editing.

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Correspondence to Shahrokh F. Shariat.

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Kimura, S., D’Andrea, D., Iwata, T. et al. Expression of urokinase-type plasminogen activator system in non-metastatic prostate cancer. World J Urol 38, 2501–2511 (2020). https://doi.org/10.1007/s00345-019-03038-5

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Keywords

  • Biochemical recurrence
  • Prostate cancer
  • Radical prostatectomy
  • Urokinase-type plasminogen activator