Up-regulation of POM121 is linked to prostate cancer aggressiveness and serves as a prognostic biomarker

Urol Oncol. 2022 Aug;40(8):380.e11-380.e18. doi: 10.1016/j.urolonc.2022.05.019. Epub 2022 Jun 17.

Abstract

Purpose: Nucleoporins as components of the nuclear pore complex (NCP) are known for regulating nuclear-cytoplasmatic transport. Recently, the nucleoporin POM121 was found to have an important impact on intranuclear translocation of prostate cancer (PCa)-specific tumor drivers including the androgen receptor (AR). The aim of our study was to assess the potential of POM121 as a prognostic biomarker.

Methods: Therefore, we performed immunohistochemistry (IHC) for POM121 on a large clinically, well characterized PCa tissue cohort comprising benign prostatic samples, radical prostatectomy (RPE) samples, lymph node metastases, local recurrent tumors and distant metastases of 289 patients. Using a semi automated tissue image analysis software we evaluated POM121 protein expression level based on IHC.

Results: We could show that POM121 expression increases during tumor progression. Expression levels were significantly higher in primary tumors compared to benign samples (P = 0.001), and substantially higher in advanced tumors (P < 0.001) and in distant metastases (P = 0.006) compared to primary tumors. Furthermore, POM121 expression predicts biochemical recurrence free survival (BFS) after surgery independent of the WHO group and other clinicopathological markers. 5-years BFS with primary tumors lacking POM121 and expressing POM121 was 88.8% and 68.9%, respectively.

Conclusion: Our study reveals the potential of POM121 as a potential biomarker for PCa, predicting BFS independent of other common clinicopathological parameters. Furthermore, POM121 might be a new targetable structure for patients suffering from advanced PCa.

Keywords: Androgen receptor; Biomarker; Nuclear pore complex; Nucleoporins; POM121; Prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Male
  • Membrane Glycoproteins / metabolism
  • Prognosis
  • Prostatectomy
  • Prostatic Neoplasms* / pathology
  • Up-Regulation

Substances

  • Membrane Glycoproteins
  • POM121 protein, human

Supplementary concepts

  • Prostate Cancer, Hereditary, 7