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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Burdelski, Christoph Menan, Devi Tsourlakis, Maria Christina Kluth, Martina Hube-Magg, Claudia Melling, Nathaniel Minner, Sarah Koop, Christina Graefen, Markus Heinzer, Hans Wittmer, Corinna Sauter, Guido Simon, Ronald Schlomm, Thorsten Steurer, Stefan Krech, Till |
| Abstract | Background Posttranscriptional 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. Methods SENP1 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. Results SENP1 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. Conclusions SENP1 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. |
| Related Links | https://bmccancer.biomedcentral.com/counter/pdf/10.1186/s12885-015-1555-8.pdf |
| Ending Page | 13 |
| Page Count | 13 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 14712407 |
| DOI | 10.1186/s12885-015-1555-8 |
| Journal | BMC Cancer |
| Issue Number | 1 |
| Volume Number | 15 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2015-07-23 |
| Access Restriction | Open |
| Subject Keyword | Cancer Research Oncology Surgical Oncology Health Promotion and Disease Prevention Biomedicine Medicine Public Health Prostate cancer ERG fusion PTEN deletion SENP1 SUMO Immunohistochemistry Tissue microarray Medicine/Public Health |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Oncology Genetics |
| Journal Impact Factor | 3.4/2023 |
| 5-Year Journal Impact Factor | 3.8/2023 |
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