Abstract 4826: Cancer/testis antigen expression pattern is a potential biomarker for prostate cancer aggressiveness

Abstract

Abstract Introduction: The prostate-specific antigen (PSA) test has improved the early detection of PCa and also recurrence after radical prostatectomy (RP). However, it is estimated that 35% of patients submitted to RP that progress with detectable PSA levels will never present metastatic disease. Thus, there is a need to distinguish localized curable disease from a subset of patients at risk for progression. Currently, the D’Amico Stratification System defines high risk PCa as any combination of the following factors: PSA >20ng/ml, a Gleason score (GS) of 8-10, or clinical stage T2c or greater. As some aggressive PCa did not fit these criteria, a more accurate test to classify high risk patients is crucial. Objective: The objective of this study is to identify a cancer/testis antigen (CTA)-based biomarker to discern PCa patients with potentially aggressive disease. The CTAs are a unique group of genes whose expression is normally confined to germ cells in normal testis and placenta, but aberrantly expressed in several types of cancers. Methods and results: Using Nanostring multiplex approach, we screened the expression of 22 CTA genes in 20 localized (LPCa) and 20 metastatic prostate cancer (MPCa) samples, obtained from University of Washington. Using ROC curve analysis we ranked the CTAs capable of discriminating LPCa and MPCa. We found one under-expressed CTA (PAGE4) and seven over-expressed (CEP55, NUF2, PBK, RQCD1, SPAG4, SSX2 and TTK) in MPCa, considering AUC>0.70. qRT-PCR was used to validate Nanostring results in the same set of samples and to identify the candidate CTA biomarkers. The eight CTAs selected showed significant expression changes and were also capable of separating LPCa and MPCa cases (AUC>0.70). A multivariate logistic regression model (MLR) showed that combined expression patterns of CEP55, NUF2, PBK and TTK was capable of discriminating MPCa from LPCa with AUC = 0.95 (pr = 0.15), sensitivity = 80%, specificity = 90%. Using this model 85% of the PCa cases were correctly classified. We then evaluated, by q-RT-PCR, if CTA expression profile is associated with GS using the same 20 LPCa samples and a new set of 25 PCa samples. The PCa cases were separated in two groups according to GS: (1) 3+3/3+4 and (2) other GS. The expression pattern of the CTA panel CEP55, NUF2 and RQCD1 correctly separated 83% of the samples according to the GS with AUC = 0.89 (pr = 0.05), sensitivity = 88%, specificity 75%. Conclusion: The results of the study are clinically and biologically relevant, since little is known about the role of CTAs in PCa. The CTA expression pattern was shown to be different between two extreme pathologic phenotypes and also among samples of different GS. The CTA profile may be useful to identify high risk LPCa patients and to stratify patients according to GS, which may guide treatment strategies for the different groups of patients. Citation Format: Luciane T. Kagohara, Prakash Kulkarni, Takumi Shiraishi, Guangjing Zhu, Robert Vessella, Robert Veltri. Cancer/testis antigen expression pattern is a potential biomarker for prostate cancer aggressiveness. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4826. doi:10.1158/1538-7445.AM2015-4826