Cancer/testis antigens: novel tools for discerning aggressive and non-aggressive prostate cancer

Abstract

The introduction of serum prostate-specific antigen (PSA) in the 1980s has dramatically altered and benefited the initial diagnosis of prostate cancer. However, the widespread use of PSA testing has resulted in overdetection and overtreatment of potentially indolent disease. Thus, a clinical dilemma today in the management of prostate cancer is to discern men with aggressive disease who need definitive treatment from men whose disease are not lethal. Although several serum and tissue biomarkers have been evaluated during the past decade, improved markers are still needed to enhance the accuracy, with which patients at risk can be discerned and treated more aggressively. The cancer/testis antigens (CTAs) are a group of proteins that are restricted to the testis in the normal adult, but are aberrantly expressed in several types of cancers. Because of their restricted expression pattern, the CTAs represent attractive biomarker candidates for cancer diagnosis/prognosis. Furthermore, several studies to date have reported the differential expression of CTAs in prostate cancer. Here, we review recent developments that demonstrate the potential of the CTAs as biomarkers to discern the aggressive phenotype of prostate cancer.

Figure 1

The MAGEA/CSAG cancer/testis antigen subfamilies are coordinately upregulated in castrate-resistant prostate cancer. Primary prostate cancer samples were obtained from radical prostatectomy while castrate-resistant prostate cancer were obtained from ‘rapid' autopsies and propagated as xenografts. RNA samples were run on a whole genome microarray. Heat map shows the predominant upregulation of MAGEA genes as well as the CSAG genes. The color display is on a 10-fold scale and red indicates overexpression relative to BPH. Green indicates downregulation. Adapted from Ref. 38. PCa, prostate cancer.

Figure 2

CTA expression in recurrent and non-recurrent prostate cancer. CTA expression of (a) CEP55, (b) NUF2 and (c) PAGE4 in clinically localized prostate cancer with recurrence (Rec (+)) (n=43) and without recurrence (Rec (−)) (n=29), were examined using multiplexed quantitative real time PCR. Adapted from Ref. 39. For details of the method, see Ref. 39. CTA, cancer/testis antigen.

Figure 3

Kaplan–Meier analyses. Kaplan–Meier curves showing biochemical recurrence-free survival against time after radical prostatectomy stratified by the mRNA expression of (a) CEP55, (b) NUF2 and (c) PAGE4 (high versus low groups dichotomized by median value). Adapted from Ref. 39. For details of the method, see Ref. 39.