The prognostic value of SUMO1/Sentrin specific peptidase 1 (SENP1) in prostate cancer is limited to ERG-fusion positive tumors lacking PTEN deletion

Abstract

BackgroundPosttranscriptional protein modification by SUMOylation plays an important role in tumor development and progression. In the current study we analyzed prevalence and prognostic impact of the de-SUMOylation enzyme SENP1 in prostate cancer.MethodsSENP1 expression was analyzed by immunohistochemistry on a tissue microarray containing more than 12,400 prostate cancer specimens. Results were compared to tumor phenotype, ERG status, genomic deletions of 3p, 5q, 6q and PTEN, and biochemical recurrence.ResultsSENP1 immunostaining was detectable in 34.5 % of 9,516 interpretable cancers and considered strong in 7.3 %, moderate in 14.9 % and weak in 12.3 % of cases. Strong SENP1 expression was linked to advanced pT stage (p < 0.0001), high Gleason grade (p < 0.0001), positive lymph node status (p = 0.0019), high pre-operative PSA levels (p = 0.0037), and PSA recurrence (p < 0.0001). SENP1 expression was strongly associated with positive ERG fusion status as determined by both in situ hybridization (FISH) and immunohistochemistry as well as with PTEN deletions. Detectable SENP1 immunostaining was found in 41 % of ERG positive and in 47 % of PTEN deleted cancers but in only 30 % of ERG negative and 30 % of PTEN non-deleted cancers (p < 0.0001 each). Deletions of 3p, 5q, and 6q were unrelated to SENP1 expression. Subset analyses revealed that the prognostic impact of SENP1 expression was solely driven by the subgroup of ERG positive, PTEN undeleted cancers. In this subgroup, the prognostic role of SENP1 expression was independent of the preoperative PSA level, tumor stage, Gleason grade, and the status of the resection margin.ConclusionsSENP1 expression has strong prognostic impact in a molecularly defined subset of cancers. This is per se not surprising as the biologic impact of each individual molecular event is likely to be dependent on its cellular environment. However, such findings challenge the concept of finding clinically relevant molecular signatures that are equally applicable to all prostate cancers.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1555-8) contains supplementary material, which is available to authorized users.

Loss of cytoplasmic survivin expression is an independent predictor of poor prognosis in radically operated prostate cancer patients

“…PTEN deletions are linked to poor prognosis in PCa . Many prognostic features fail to further stratify patient outcome in molecular subgroups that are already defined by PTEN deletion . The significant link between low‐level survivin staining and tumor proliferation would be consistent with a role of survivin expression in the control of cellular proliferation as suggested by several authors .…”

SENP1, but not fetal hemoglobin, differentiates Andean highlanders with chronic mountain sickness from healthy individuals among Andean highlanders

“…Higher SENP1 expression has been hypothesized to be associated with higher androgen activity in Andean highlanders with EE [34]. Higher expression of SENP1 has been documented to induce HIF-1α and reduce apoptosis, thus promoting the development or progression of prostate [35] and other cancer [36,37] cells. Recently, absence of SENP1 has been reported to produce inflammatory cytokines, leading to type 1 diabetes in a murine model [38], and reduced expression led to impaired glucosedependent insulin exocytosis in an in vitro human islet model [39].…”

Depletion of SENP1 suppresses the proliferation and invasion of triple-negative breast cancer cells

“…Previously, many studies reported that SENP1 was overexpressed in human prostate cancer (CaP) cells (9), as well as lung cancer tissues (10) and most of colon cancer tissues (11). The expression of SENP1 was reported to have strong prognostic impact on a molecularly defined subset of CaPs (12). Another study revealed that SENP1 might be a prognostic marker and a therapeutic target for metastasis in CaP patients, for its roles in regulating MMP2 and MMP9 through the HIF-1α signaling pathway (13).…”