Splice variant transcripts of the anterior gradient 2 gene as a marker of prostate cancer
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Antje Neeb1,*, Simon Hefele2,*, Stefanie Bormann1,8, Walther Parson3,4, Fabian Adams5, Philipp Wolf5, Arkadiusz Miernik5, Martin Schoenthaler5, Malte Kroenig5, Konrad Wilhelm5, Wolfgang Schultze-Seemann5, Sigrun Nestel6, Georg Schaefer7, Huajie Bu7, Helmut Klocker7, Irina Nazarenko2,* and Andrew C. B. Cato1,*
1 Karlsruhe Institute of Technology, Institute of Toxicology and Genetics, Eggenstein-Leopoldshafen, Germany
2 Department of Environmental Health Sciences and Hospital Infection Control, Medical Center-University of Freiburg, Freiburg, Germany
3 Institute of Legal Medicine, Innsbruck Medical University, Innsbruck, Austria
4 Penn State Eberly College of Science, University Park, PA, USA
5 Department of Urology, Medical Center-University of Freiburg, Freiburg, Germany
6 Institute of Anatomy and Cell Biology, University of Freiburg, Freiburg, Germany
7 Department of Urology, Division of Experimental Urology, Innsbruck Medical University, Innsbruck, Austria
8 Heinrich Heine University, Institute of Toxicology, Düsseldorf, Germany
* These authors contributed equally to this work
Antje Neeb, email:
Irina Nazarenko, email:
Keywords: Anterior gradient 2 gene, Exosomes, Prostate cancer diagnosis, Urinary biomarkers, Splice variants
Received: June 16, 2014 Accepted: August 18, 2014 Published: August 19, 2014
Anterior gradient 2 (AGR2) is a gene predominantly expressed in mucus-secreting tissues or in endocrine cells. Its expression is drastically increased in tumors including prostate cancer. Here we investigated whether AGR2 transcript levels can be used as a biomarker to detect prostate cancer (PCa). Using a PCR-based approach, we could show that in addition to the wild-type (AGRwt long and short) transcripts, five other AGR2 splice variants (SV) (referred to as AGR2 SV-C, -E, -F, -G and -H) were present in cancer cell lines. In tissue biopsies, SV-H and AGR2wt (short) distinguished between benign and PCa (p ≤ 0.05 n = 32). In urine exosomes, AGR2 SV-G and SV-H outperformed serum PSA. Receiver operating characteristic (ROC) curves showed the highest discriminatory power of SV-G and SV-H in predicting PCa. AGR2 SV-G and SV-H are potential diagnostic biomarkers for the non-invasive detection of PCa using urine exosomes.
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