BackgroundThe Cancer/Testis Antigens (CTAs) are an important group of proteins that are typically restricted to the testis in the normal adult but are aberrantly expressed in several types of cancers. As a result of their restricted expression patterns, the CTAs could serve as unique biomarkers for cancer diagnosis/prognosis. The aim of this study was to identify promising CTAs that are associated with prostate cancer (PCa) recurrence following radical prostatectomy (RP).MethodsThe expression of 5 CTAs was measured by quantitative multiplex real-time PCR using prostate tissue samples obtained from 72 patients with apparently clinically localized PCa with a median of two years follow-up (range, 1 to 14 years).ResultsThe expression of CTAs namely, CEP55, NUF2, PBK and TTK were significantly higher while PAGE4 was significantly lower in patients with recurrent disease. All CTAs with the exception of TTK were significantly correlated with the prostatectomy Gleason score, but none were correlated with age, stage, or preoperative PSA levels. In univariate proportional hazards models, CEP55 (HR = 3.59, 95% CI: 1.50-8.60), p = 0.004; NUF2 (HR = 2.28, 95% CI: 1.11-4.67), p = 0.024; and PAGE4 (HR = 0.44, 95% CI: 0.21-0.93), p = 0.031 were significantly associated with the risk of PCa recurrence. However, the results were no longer significant after adjustment for prostatectomy Gleason score.ConclusionsTo our knowledge, this is the first study to identify CTAs as biomarkers that can differentiate patients with recurrent and non-recurrent disease following RP and underscores its potential impact on PCa prognosis and treatment.

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Background The cancer/testis antigens (CTAs) are a unique group of proteins normally expressed in germ cells but aberrantly expressed in several types of cancers including prostate cancer (PCa). However, their role in PCa has not been fully explored. Methods CTA expression profiling in PCa samples and cell lines was done utilizing a custom microarray that contained probes for two-thirds of all CTAs. The data were validated by quantitative PCR (Q-PCR). Functional studies were carried out by silencing gene expression with siRNA. DNA methylation was determined by methylation-specific PCR. Results A majority of CTAs expressed in PCa are located on the X chromosome (CT-X antigens). Several CT-X antigens from the MAGEA/CSAG subfamilies are coordinately upregulated in castrate-resistant prostate cancer (CRPC) but not in primary PCa. In contrast, PAGE4 is highly upregulated in primary PCa but is virtually silent in CRPC. Further, there was good correlation between the extent of promoter DNA methylation and CTA expression. Finally, silencing the expression of MAGEA2 the most highly upregulated member, significantly impaired proliferation of prostate cancer cells while increasing their chemosensitivity. Conclusions Considered together, the remarkable stage-specific expression patterns of the CT-X antigens strongly suggests that these CTAs may serve as unique biomarkers that could potentially be used to distinguish men with aggressive disease who need treatment from men with indolent disease not requiring immediate intervention. The data also suggest that the CT-X antigens may be novel therapeutic targets for CRPC for which there are currently no effective therapeutics.

BACKGROUND The antiangiogenic CXC chemokines interferon γ (IFN‐γ)‐inducible T‐cell α chemoattractant (I‐TAC) and monokine induced by IFN‐γ (Mig) are known as members of IFN‐γ‐inducible antiangiogenic CXC chemokines. However, the expression of these chemokines in highly angiogenic tumors remains poorly understood. The authors examined expression of I‐TAC, Mig, and their receptor, CXCR3, in tissue samples from patients with renal cell carcinoma (RCC). METHODS Twenty‐one samples of untreated RCC and corresponding normal renal tissues were obtained from surgical specimens. The expression levels of I‐TAC, Mig, and CXCR3 were investigated using reverse transcriptase‐polymerase chain reaction (RT‐PCR) analysis, real‐time RT‐PCR analysis, and Western blot analysis. Immunohistochemistry was carried out to clarify the localization of both chemokines and of CXCR3. RESULTS RT‐PCR analysis showed strong expression levels of I‐TAC, Mig, and CXCR3 in RCC tissues and very weak or undetectable expression in normal kidney tissues. Real‐time RT‐PCR analysis showed that expression levels of I‐TAC, Mig, and CXCR3 in RCC tissues were 14.9 times greater, 30.3 times greater, and 9.9 times greater compared with the levels in the corresponding normal kidney tissues, respectively (P < 0.01). Western blot analysis showed up‐regulation of I‐TAC, Mig, and CXCR3 at the protein level. Immunofluorescence double stainings revealed that I‐TAC coincided with pericytes and vascular smooth muscle cells (VSMCs) in tumor angiogenic vessels. Mig was detected in tumor endothelial cells (TECs) and in infiltrating leukocytes. In the corresponding normal kidney tissues, neither VSMCs nor endothelial cells showed positive stainings for these chemokines. CXCR3 was expressed in both tumor cells and infiltrating leukocytes. CONCLUSIONS The results revealed special feature of vascular mural cells and TECs in RCC. The up‐regulated I‐TAC and Mig, produced by tumor vessels, may interact with CXCR3 expressed in tumor cells, with possible pathophysiologic significance in RCC progression. Cancer 2005. © 2004 American Cancer Society.