Overexpression of SERBP1 (Plasminogen activator inhibitor 1 RNA binding protein) in human breast cancer is correlated with favourable prognosis.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Nuran Bektas Serce, Andreas Boesl, Irina Klaman, Sonja von Serényi, Erik Noetzel, Michael F Press, Arno Dimmler, Arndt Hartmann, Jalid Sehouli, Ruth Knuechel, Matthias W Beckmann, Peter A Fasching, Edgar Dahl
• Journal: BMC cancer (BMC Cancer) Vol. 12 Pg. 597 (Dec 13 2012) ISSN: 1471-2407 [Electronic] England
• PMID: 23236990 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• RNA-Binding Proteins
• SERBP1 protein, human

Topics

• Biomarkers, Tumor (analysis)
• Blotting, Western
• Breast Neoplasms (metabolism, mortality, pathology)
• Disease-Free Survival
• Female
• Humans
• Immunohistochemistry
• In Situ Hybridization
• Kaplan-Meier Estimate
• Prognosis
• Proportional Hazards Models
• RNA-Binding Proteins (analysis, biosynthesis)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Tissue Array Analysis