KPNA2 Expression Is an Independent Adverse Predictor of Biochemical Recurrence after Radical Prostatectomy
- 1 March 2011
- journal article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 17 (5), 1111-1121
- https://doi.org/10.1158/1078-0432.ccr-10-0081
Abstract
Purpose: To analyze rates of expression of karyopherin alpha 2 (KPNA2) in different prostate tissues and to evaluate the prognostic properties for patients with primary prostate cancer. Experimental Design: Tissue microarrays (TMA) contained 798 formalin-fixed, paraffin-embedded prostate tissue cores from two different institutes of pathology. TMAs were stained immunohistochemically for KPNA2 and NBS1. SiRNA technologies were used to inhibit KPNA2 expression in vitro, and the effect of this inhibition on cellular viability was determined. Efficiency of knockdown experiments was determined by Western blot analysis. Results: KPNA2 expression was significantly upregulated in carcinomas of the prostate, especially in metastatic and castration-resistant prostate cancer samples. Positive nuclear KPNA2 immunoreactivity was identified as a novel predictor of biochemical recurrence after radical prostatectomy (n = 348), and was independent of the well-established predictive factors preoperative PSA value, Gleason score, tumor stage, and surgical margin status. These results were validated by analyzing a second and independent prostate cancer cohort (n = 330). Further, in vitro experiments showed that the cell proliferation and viability of PC3 cells was significantly reduced when KPNA2 expression was inhibited. KPNA2 knockdown did not induce PARP cleavage as marker for apoptosis. No significantly increased sub-G1 fraction could be found by FACS analysis. Conclusions: KPNA2 is a novel independent prognostic marker for disease progression after radical prostatectomy. This allows to identify patients who need more aggressive treatment. It can moreover be speculated that patients not suited for surveillance regimens might be identified at initial biopsy by a positive KPNA2 immunohistochemistry. Clin Cancer Res; 17(5); 1111–21. ©2011 AACR.Other Versions
This publication has 27 references indexed in Scilit:
- Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostateNature Genetics, 2009
- The Karyopherin proteins, Crm1 and Karyopherin β1, are overexpressed in cervical cancer and are critical for cancer cell survival and proliferationInternational Journal of Cancer, 2009
- Nuclear karyopherin α2 expression predicts poor survival in patients with advanced breast cancer irrespective of treatment intensityInternational Journal of Cancer, 2008
- Histone deacetylases 1, 2 and 3 are highly expressed in prostate cancer and HDAC2 expression is associated with shorter PSA relapse time after radical prostatectomyBritish Journal of Cancer, 2008
- Molecular Profiling of Laser-Microdissected Matched Tumor and Normal Breast Tissue Identifies Karyopherin α2 as a Potential Novel Prognostic Marker in Breast CancerClinical Cancer Research, 2006
- Gene Expression Profiling of Primary Cutaneous Melanoma and Clinical OutcomeJNCI Journal of the National Cancer Institute, 2006
- Nijmegen Breakage Syndrome and Functions of the Responsible Protein,NBS1Genome dynamics, 2006
- Biomarkers in Cancer Staging, Prognosis and Treatment SelectionNature Reviews Cancer, 2005
- Dissection of the Karyopherin α Nuclear Localization Signal (NLS)-binding GrooveJournal of Biological Chemistry, 2003
- Tissue microarrays for high-throughput molecular profiling of tumor specimensNature Medicine, 1998