Serum Autoantibodies in Chronic Prostate Inflammation in Prostate Cancer Patients

PLoS One. 2016 Feb 10;11(2):e0147739. doi: 10.1371/journal.pone.0147739. eCollection 2016.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / blood
  • Adult
  • Aged
  • Autoantibodies / blood*
  • Autoantibodies / chemistry
  • Biopsy
  • Chronic Disease
  • False Positive Reactions
  • Humans
  • Immunohistochemistry
  • Inflammation / blood*
  • Inflammation / immunology
  • Lymphocytes / cytology
  • Male
  • Middle Aged
  • Nuclear Proteins / blood
  • Prostate / immunology*
  • Prostate-Specific Antigen / blood
  • Prostatectomy
  • Prostatic Diseases / blood*
  • Prostatic Diseases / immunology
  • Prostatic Neoplasms / blood*
  • Prostatic Neoplasms / immunology
  • Protein Array Analysis
  • Qa-SNARE Proteins / blood
  • Repressor Proteins / blood
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spastin
  • Tissue Array Analysis

Substances

  • Autoantibodies
  • Nuclear Proteins
  • Qa-SNARE Proteins
  • Repressor Proteins
  • SPOP protein, human
  • Prostate-Specific Antigen
  • Adenosine Triphosphatases
  • Spastin
  • SPAST protein, human

Grant support

The study was supported by COMET K1 Center Oncotyrol—Center for Personalized Medicine, financed by the Austrian Research Promotion Agency (FFG) and the Future Foundation of the Country of Tyrol, and Protagen AG. ONCOTYROL GmbH, Protagen AG and TARGOS Molecular Pathology GmbH provided support in the form of salaries for authors [BS, PM, GS], [AL, KM, CT, PA, SM, PSK], [DZ, MK] but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. All other authors declare no competing interest. The specific roles of these authors are articulated in the ‘author contributions’ section.