title: Serum Autoantibodies in Chronic Prostate Inflammation in Prostate Cancer Patients.
abstract: BACKGROUND
  Chronic inflammation is frequently observed on histological analysis of malignant and non-malignant prostate specimens. It is a suspected supporting factor for prostate diseases and their progression and a main cause of false positive PSA tests in cancer screening. We hypothesized that inflammation induces autoantibodies, which may be useful biomarkers. We aimed to identify and validate prostate inflammation associated serum autoantibodies in prostate cancer patients and evaluate the expression of corresponding autoantigens.
  
  
  METHODS
  Radical prostatectomy specimens of prostate cancer patients (N = 70) were classified into high and low inflammation groups according to the amount of tissue infiltrating lymphocytes. The corresponding pre-surgery blood serum samples were scrutinized for autoantibodies using a low-density protein array. Selected autoantigens were identified in prostate tissue and their expression pattern analyzed by immunohistochemistry and qPCR. The identified autoantibody profile was cross-checked in an independent sample set (N = 63) using the Luminex-bead protein array technology.
  
  
  RESULTS
  Protein array screening identified 165 autoantibodies differentially abundant in the serum of high compared to low inflammation patients. The expression pattern of three corresponding antigens were established in benign and cancer tissue by immunohistochemistry and qPCR: SPAST (Spastin), STX18 (Syntaxin 18) and SPOP (speckle-type POZ protein). Of these, SPAST was significantly increased in prostate tissue with high inflammation. All three autoantigens were differentially expressed in primary and/or castration resistant prostate tumors when analyzed in an inflammation-independent tissue microarray. Cross-validation of the inflammation autoantibody profile on an independent sample set using a Luminex-bead protein array, retrieved 51 of the significantly discriminating autoantibodies. Three autoantibodies were significantly upregulated in both screens, MUT, RAB11B and CSRP2 (p>0.05), two, SPOP and ZNF671, close to statistical significance (p = 0.051 and 0.076).
  
  
  CONCLUSIONS
  We provide evidence of an inflammation-specific autoantibody profile and confirm the expression of corresponding autoantigens in prostate tissue. This supports evaluation of autoantibodies as non-invasive markers for prostate inflammation.
authors: Division of Experimental Urology, Dept. of Urology, Medical University of Innsbruck, Innsbruck, Austria.|ONCOTYROL, Center for Personalized Cancer Medicine, Innsbruck, Austria.
authors: Bettina
authors: B
authors: Schlick
authors: Division of Experimental Urology, Dept. of Urology, Medical University of Innsbruck, Innsbruck, Austria.|ONCOTYROL, Center for Personalized Cancer Medicine, Innsbruck, Austria.
authors: Petra
authors: P
authors: Massoner
authors: Protagen AG, Dortmund, Germany.
authors: Angelika
authors: A
authors: Lueking
authors: Division of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria.
authors: Pornpimol
authors: P
authors: Charoentong
authors: Department of Pathology and Laboratory Medicine, Institute of Precision Medicine, Weill Medical College of Cornell University, New York, NY, United States of America.
authors: Mirjam
authors: M
authors: Blattner
authors: ONCOTYROL, Center for Personalized Cancer Medicine, Innsbruck, Austria.|Department of Pathology, Medical University of Innsbruck, Innsbruck, Austria.
authors: Georg
authors: G
authors: Schaefer
authors: Protagen AG, Dortmund, Germany.
authors: Klaus
authors: K
authors: Marquart
authors: Protagen AG, Dortmund, Germany.
authors: Carmen
authors: C
authors: Theek
authors: Protagen AG, Dortmund, Germany.
authors: Peter
authors: P
authors: Amersdorfer
authors: TARGOS Molecular Pathology GmbH, Kassel, Germany.
authors: Dirk
authors: D
authors: Zielinski
authors: TARGOS Molecular Pathology GmbH, Kassel, Germany.
authors: Matthias
authors: M
authors: Kirchner
authors: Division of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria.
authors: Zlatko
authors: Z
authors: Trajanoski
authors: Department of Pathology and Laboratory Medicine, Institute of Precision Medicine, Weill Medical College of Cornell University, New York, NY, United States of America.
authors: Mark A
authors: MA
authors: Rubin
authors: Protagen AG, Dortmund, Germany.
authors: Stefan
authors: S
authors: Müllner
authors: Protagen AG, Dortmund, Germany.
authors: Peter
authors: P
authors: Schulz-Knappe
authors: Division of Experimental Urology, Dept. of Urology, Medical University of Innsbruck, Innsbruck, Austria.
authors: Helmut
authors: H
authors: Klocker
mesh_terms: D000251:Adenosine Triphosphatases / Q000097:blood; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood* / Q000737:chemistry; D001706:Biopsy; D002908:Chronic Disease; D005189:False Positive Reactions; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000097:blood* / Q000276:immunology; D008214:Lymphocytes / Q000166:cytology; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000097:blood; D011467:Prostate / Q000276:immunology*; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011469:Prostatic Diseases / Q000097:blood* / Q000276:immunology; D011471:Prostatic Neoplasms / Q000097:blood* / Q000276:immunology; D040081:Protein Array Analysis; D050765:Qa-SNARE Proteins / Q000097:blood; D012097:Repressor Proteins / Q000097:blood; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000074181:Spastin; D046888:Tissue Array Analysis
chemical_list: D001323:Autoantibodies; D009687:Nuclear Proteins; D050765:Qa-SNARE Proteins; D012097:Repressor Proteins; C509761:SPOP protein, human; D017430:Prostate-Specific Antigen; D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human