Abstract 4525: Cancer/testis antigens: A biomarker panel for prostate cancer screening

Abstract

Abstract The aim of the current study was to identify a panel of cancer/testis antigens (CTAs) with the potential to be used as a complementary test to the prostate-specific antigen (PSA) test for prostate cancer (PCa) screening. PSA test is capable of identifying men under risk of PCa before the presence of symptoms. However, this screening has been considered a controversy assessment since many men presenting benign lesions (benign prostate hyperplasia or other inflammatory conditions) can also present increased PSA levels. Hence, the great current dilemma in PCa screening is to develop a test that in combination with PSA assay could present higher accuracy for PCa early diagnosis. CTAs constitute an important class of potential cancer biomarkers that are poorly studied in PCa. CTAs are normally expressed in testis and germ cells and are aberrantly over-expressed in cancers. This unique pattern of expression makes these genes potential candidates as specific tumor biomarkers. CTA aberrant expression in malignant tumors is associated with phenotypic changes that confer the cancer cells essential advantages for proliferation and survival. Our hypothesis is that a panel of CTAs differentially expressed in PCa compared to normal prostate tissue would be useful to develop a diagnostic biomarker panel to be used in combination with the PSA test. We initially evaluated the expression of 22 CTAs, using the Nanostring approach, in localized and metastatic PCa to identify those genes associated with more aggressive tumors. After validation by qRT-PCR, we verified that 8 genes were differentially expressed between indolent and aggressive tumors. Using immunohistochemistry and a quantitative image analysis to measure protein expression, we evaluated CTA protein levels in PCa and adjacent normal tissue paired samples. The CTAs CEP55, NUF2, PAGE4, PBK, RQCD1, SPAG4, SSX2 and TTK presented increased protein levels in PCa when compared to normal prostate tissue from the same patient. Increased levels of PAGE4, PBK, RQCD1, SPAG4 and SSX2 were more frequent among patients with Gleason Score 4+3 or higher. In an attempt to identify a panel of CTAs with increased expression in PCa vs. prostate normal samples, we used multiple logistic regression analysis (MLR). MLR analysis showed that a panel that includes all 8 CTAs analyzed correctly classified 88.9% of the cases (AUC=0.96; sensitivity=88.5%; specificity=89.2%). For the MLR analysis, we considered the intensity and the frequency of the cancer cells with positive CTA expression. The intensity of all 8 CTAs was significant in the analysis, while the frequency of staining was only relevant for NUF2, PBK, SSX2 and TTK. Our findings suggest that our 8 CTAs panel represent a potential biomarker with high accuracy to discriminate normal prostate from PCa. Further studies to evaluate their expression in bodily fluids will determine their potential as a non-invasive PCa screening test to be used in combination with PSA. Citation Format: Luciane T. Kagohara, Prakash Kulkarni, Takumi Shiraishi, Robert Vessella, Robert W. Veltri, Elana J. Fertig. Cancer/testis antigens: A biomarker panel for prostate cancer screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4525.