title: Splice variant transcripts of the anterior gradient 2 gene as a marker of prostate cancer.
abstract: 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.
authors.affiliation: Karlsruhe Institute of Technology, Institute of Toxicology and Genetics, Eggenstein-Leopoldshafen, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Neeb
authors.affiliation: Department of Environmental Health Sciences and Hospital Infection Control, Medical Center-University of Freiburg, Freiburg, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Hefele
authors.affiliation: Karlsruhe Institute of Technology, Institute of Toxicology and Genetics, Eggenstein-Leopoldshafen, Germany. Heinrich Heine University, Institute of Toxicology, Düsseldorf, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Bormann
authors.affiliation: Institute of Legal Medicine, Innsbruck Medical University, Innsbruck, Austria. Penn State Eberly College of Science, University Park, PA, USA.
authors.forename: Walther
authors.initials: W
authors.lastname: Parson
authors.affiliation: Department of Urology, Medical Center-University of Freiburg, Freiburg, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Adams
authors.affiliation: Department of Urology, Medical Center-University of Freiburg, Freiburg, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Wolf
authors.affiliation: Department of Urology, Medical Center-University of Freiburg, Freiburg, Germany.
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Miernik
authors.affiliation: Department of Urology, Medical Center-University of Freiburg, Freiburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Schoenthaler
authors.affiliation: Department of Urology, Medical Center-University of Freiburg, Freiburg, Germany.
authors.forename: Malte
authors.initials: M
authors.lastname: Kroenig
authors.affiliation: Department of Urology, Medical Center-University of Freiburg, Freiburg, Germany.
authors.forename: Konrad
authors.initials: K
authors.lastname: Wilhelm
authors.affiliation: Department of Urology, Medical Center-University of Freiburg, Freiburg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schultze-Seemann
authors.affiliation: Institute of Anatomy and Cell Biology, University of Freiburg, Freiburg, Germany.
authors.forename: Sigrun
authors.initials: S
authors.lastname: Nestel
authors.affiliation: Department of Urology, Division of Experimental Urology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Schaefer
authors.affiliation: Department of Urology, Division of Experimental Urology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Huajie
authors.initials: H
authors.lastname: Bu
authors.affiliation: Department of Urology, Division of Experimental Urology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Helmut
authors.initials: H
authors.lastname: Klocker
authors.affiliation: Department of Environmental Health Sciences and Hospital Infection Control, Medical Center-University of Freiburg, Freiburg, Germany.
authors.forename: Irina
authors.initials: I
authors.lastname: Nazarenko
authors.affiliation: Karlsruhe Institute of Technology, Institute of Toxicology and Genetics, Eggenstein-Leopoldshafen, Germany.
authors.forename: Andrew C B
authors.initials: AC
authors.lastname: Cato
mesh_terms: D000368:Aged; D017398:Alternative Splicing; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics* / Q000652:urine; D001706:Biopsy; D045744:Cell Line, Tumor; D055354:Exosomes / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007610:Kallikreins / Q000097:blood; D008297:Male; D008875:Middle Aged; D009088:Mucoproteins; D015513:Oncogene Proteins; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000652:urine; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000652:urine; D012372:ROC Curve
chemical_list: C502296:AGR2 protein, human; D014408:Biomarkers, Tumor; D009088:Mucoproteins; D015513:Oncogene Proteins; D011506:Proteins; D012333:RNA, Messenger; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen