Serum Autoantibodies in Chronic Prostate Inflammation in Prostate Cancer Patients

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.

PloS one. 2016 Feb 10*** epublish ***

Bettina Schlick, Petra Massoner, Angelika Lueking, Pornpimol Charoentong, Mirjam Blattner, Georg Schaefer, Klaus Marquart, Carmen Theek, Peter Amersdorfer, Dirk Zielinski, Matthias Kirchner, Zlatko Trajanoski, Mark A Rubin, Stefan Müllner, Peter Schulz-Knappe, Helmut Klocker

Division of Experimental Urology, Dept. of Urology, Medical University of Innsbruck, Innsbruck, Austria. , Division of Experimental Urology, Dept. of Urology, Medical University of Innsbruck, Innsbruck, Austria. , Protagen AG, Dortmund, Germany. , Division of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria. , Department of Pathology and Laboratory Medicine, Institute of Precision Medicine, Weill Medical College of Cornell University, New York, NY, United States of America. , ONCOTYROL, Center for Personalized Cancer Medicine, Innsbruck, Austria. , Protagen AG, Dortmund, Germany. , Protagen AG, Dortmund, Germany. , Protagen AG, Dortmund, Germany. , TARGOS Molecular Pathology GmbH, Kassel, Germany. , TARGOS Molecular Pathology GmbH, Kassel, Germany. , Division of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria. , Department of Pathology and Laboratory Medicine, Institute of Precision Medicine, Weill Medical College of Cornell University, New York, NY, United States of America. , Protagen AG, Dortmund, Germany. , Protagen AG, Dortmund, Germany. , Division of Experimental Urology, Dept. of Urology, Medical University of Innsbruck, Innsbruck, Austria.

PubMed

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