Abstract A37: Low-density protein array reveals inflammation associated serum-autoantibody profile in prostate cancer.

Abstract

Abstract Background: Chronic prostatic inflammation of the prostate is one of the main reasons for false positive serum PSA tests in prostate cancer screening. In addition there is accumulating evidence that an inflammatory microenvironment may support the development of malignancy and the progression to metastatic disease. Easy accessible and non-invasive indicators for prostate inflammation would be very helpful for a biopsy decision after an elevated PSA test result. However, at present, the histological examination of prostate biopsies remains the only way for identification of prostatic inflammation. The finding that cancer is immunogenic and that patients are able to elicit and potentially amplify an immune response against their tumor antigens suggests that autoantibodies serve as non-invasive serum biomarkers for prostate cancer diagnosis. Consequently, autoantibodies may also be capable of detecting differential disease progression grades -e.g. inflammatory states- enabling a more specific and individualized treatment in cancer therapy. In the present study, we aimed to find new non-invasive biomarkers for the diagnosis of prostatic inflammation in prostate cancer. Methods: Seventy prostate cancer tissue samples derived from radical prostatectomy were classified into two groups (high/low inflammation) according to the amount of tissue infiltrating lymphocytes. Clinical parameters including PSA, fPSA, GSC, prostate weight, prostate volume, tumor size, age and CRP were controlled for equal distribution amongst the two groups. The corresponding blood serum samples were analyzed using a low density protein array (microarray) containing 4012 prostate cancer associated and inflammation related recombinant proteins. Statistical comparison of the serum autoantibody profile in the two groups was used to identify differentially expressed biomarkers. Finally, specificity of candidate autoantibody markers was validated by immunohistochemical detection of corresponding autoantigens in prostate tissue. Results: Autoantibodies against 165 antigens were found to be differentially expressed in the high compared to the low inflammation group. 30 out of these proteins have recently been identified to be associated with prostate cancer. The identified autoantibody profile discriminated between prostate cancer patients bearing high or low inflammation in prostate tissue with a ROC curve AUC of 0.71. Out of the top ranked autoantibodies, three candidate proteins were selected due to their differential expression and significant up-regulation in serum samples of the high inflammation group: SPAST (Spastin), STX18 (Syntaxin 18) and SPOP (speckle-type POZ protein). Immunohistochemical analysis showed that targets of all three autoantibody candidates are expressed in epithelial prostate cells. Remarkably, the highest staining intensity was detected in tissue infiltrating lymphocytes in both high and low inflammation samples. Conclusion: The presented data evaluates the possible use of serum autoantibody markers as non-invasive indicators for the diagnosis of chronic inflammation in prostate cancer. The polyclonal immune response to aberrant proteins in heterogeneous diseases such as cancer and autoimmunity favors the development of autoantibody markers with potential specificities to detect disease subtypes and disease progression grades. We provide evidence for an inflammation specific antibody profile and verify the expression of three biomarker candidates in prostate tissue. Citation Format: Bettina Schlick, Petra Massoner, Angelika Luecking, Christof Saifarth, Georg Schaefer, Klaus Marquart, Peter Amersdorfer, Peter Schulz-Knappe, Helmut Klocker. Low-density protein array reveals inflammation associated serum-autoantibody profile in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr A37.