Prognostic impact of SUMO-specific protease 1 (SENP1) in prostate cancer patients undergoing radical prostatectomy

Urol Oncol. 2013 Nov;31(8):1539-45. doi: 10.1016/j.urolonc.2012.03.007. Epub 2012 Oct 22.

Abstract

Objectives: To investigate small ubiquitin-like modifier (SUMO)-specific protease 1 (SENP1) expression in human prostate cancer (CaP) cells and its prognostic value for CaP patients after radical prostatectomy (RP).

Materials and methods: SENP1 expression in CaP cells was detected by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blotting. By using immunohistochemistry coupled with the tissue microarray (TMA) technique, we examined SENP1 protein expression in 115 specimens of CaP, 19 prostatic intra-epithelial neoplasia (PIN) tissues, and 24 normal prostate tissues. Moreover, correlations between SENP1 protein expression, clinicopathologic features, and prognosis were statistically analyzed.

Results: Three CaP cells, DU145, PC-3, and LNCaP had overexpression of SENP1 mRNA and protein, while the nontransformed immortalized prostate cell RWPE-1 had relatively weak SENP1 expression. Especially, DU145, a hormone-independent CaP cell line, showed higher transcriptional and translational level of SENP1 than the others. SENP1 protein expression correlated with some clinicopathologic parameters, such as pathologic stage, Gleason score, and biochemical recurrence (BCR). Positive SENP1 immunostaining in the CaP, PIN, and normal prostate tissue samples were 76.5%, 57.9%, and 4.2%, respectively. CaP patients undergoing RP with positive SENP1 expression were significantly associated with poor biochemical-free survival. Multivariate analysis indicated that SENP1 protein expression was an independent prognostic factor for BCR-free survival after RP.

Conclusions: This study confirmed the up-regulation of SENP1 mRNA and protein level in CaP cells. We suggested that SENP1 expression might contribute to the malignant progression of CaP. Importantly, SENP1 presented as a potential prognostic factor for BCR after RP.

Keywords: Biochemical recurrence; Immunohistochemistry; Prostate cancer; Radical prostatectomy; SUMO-specific protease 1; Tissue microarray.

MeSH terms

  • Aged
  • Blotting, Western
  • Cell Line
  • Cell Line, Tumor
  • Cysteine Endopeptidases
  • Disease Progression
  • Disease-Free Survival
  • Endopeptidases / genetics
  • Endopeptidases / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Recurrence, Local
  • Prognosis
  • Prostate / metabolism
  • Prostate / pathology
  • Prostate / surgery*
  • Prostatectomy / methods*
  • Prostatic Intraepithelial Neoplasia / diagnosis
  • Prostatic Intraepithelial Neoplasia / surgery
  • Prostatic Neoplasms / diagnosis
  • Prostatic Neoplasms / surgery*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Array Analysis

Substances

  • Endopeptidases
  • SENP1 protein, human
  • Cysteine Endopeptidases