Overexpression of SERBP1 (Plasminogen activator inhibitor 1 RNA binding protein) in human breast cancer is correlated with favourable prognosis
1 Department of Pathology, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany
2 Department of Pathology, Vorarlberger Krankenhaus-Betriebsgesellschaft m.b.H. Hospital, Feldkirch, Austria
3 Signature Diagnostics AG, Voltaireweg 4b, 14469, Potsdam, Germany
4 Molecular Oncology Group, Institute of Pathology, University Hospital of the RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany
5 Department of PathologyKeck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, Los Angeles, CA, 90033, U.S.A
6 Department of Pathology, St.-Vincentius-Kliniken, Südenstr. 37, 76137, Karlsruhe, Germany
7 Department of Pathology, University Hospital Erlangen, Krankenhausstrasse 12, 91054, Erlangen, Germany
8 Department of Gynaecology, Charité Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany
9 Department of Gynaecology, University Hospital Erlangen, Universitätsstrasse 21-23, 91054, Erlangen, Germany
10 David Geffen School of Medicine, Division of Hematology and Oncology, University of California at Los Angeles, Los Angeles, USA
BMC Cancer 2012, 12:597 doi:10.1186/1471-2407-12-597Published: 13 December 2012
Plasminogen activator inhibitor 1 (PAI-1) overexpression is an important prognostic and predictive biomarker in human breast cancer. SERBP1, a protein that is supposed to regulate the stability of PAI-1 mRNA, may play a role in gynaecological cancers as well, since upregulation of SERBP1 was described in ovarian cancer recently. This is the first study to present a systematic characterisation of SERBP1 expression in human breast cancer and normal breast tissue at both the mRNA and the protein level.
Using semiquantitative realtime PCR we analysed SERBP1 expression in different normal human tissues (n = 25), and in matched pairs of normal (n = 7) and cancerous breast tissues (n = 7). SERBP1 protein expression was analysed in two independent cohorts on tissue microarrays (TMAs), an initial evaluation set, consisting of 193 breast carcinomas and 48 normal breast tissues, and a second large validation set, consisting of 605 breast carcinomas. In addition, a collection of benign (n = 2) and malignant (n = 6) mammary cell lines as well as breast carcinoma lysates (n = 16) were investigated for SERBP1 expression by Western blot analysis. Furthermore, applying non-radioisotopic in situ hybridisation a subset of normal (n = 10) and cancerous (n = 10) breast tissue specimens from the initial TMA were analysed for SERBP1 mRNA expression.
SERBP1 is not differentially expressed in breast carcinoma compared to normal breast tissue, both at the RNA and protein level. However, recurrence-free survival analysis showed a significant correlation (P = 0.008) between abundant SERBP1 expression in breast carcinoma and favourable prognosis. Interestingly, overall survival analysis also displayed a tendency (P = 0.09) towards favourable prognosis when SERBP1 was overexpressed in breast cancer.
The RNA-binding protein SERBP1 is abundantly expressed in human breast cancer and may represent a novel breast tumour marker with prognostic significance. Its potential involvement in the plasminogen activator protease cascade warrants further investigation.