Jay Sulek, Eka Goliadze, Shaoqing Zhou, Masoud H Manjili, Amir Toor and Georgi Guruli
Background: Cancer/testis antigens (CTA) are aberrantly expressed in various tumors, including urologic malignancies. Decreased expression of these highly immunogenic antigens might confer low immunogenicity, allowing tumors to escape immune monitoring and grow unimpeded. We obtained tissue from surgical specimens of patients with kidney and bladder cancers and compared the expression of various CTA in tumor and non-tumor specimens. Methods and Findings: Surgical specimens from radical nephrectomies and cystectomies were obtained from the Virginia Commonwealth University’s tissue bank. Quantitative polymerase chain reaction was performed to compare CTA expression in normal and tumor tissues. Expression of CTA was significantly increased in high grade kidney tumors compared to normal tissues (p<0.001) and compared to low grade tumors (P<0.001). Comparing expression in Fuhrman grade IV tumors to expression of tumors with Fuhrman grades I-III, 12 of the 13 CTA studied – SSX2 (P<0.001), SPA17 (P=0.024), CEP55 (P<0.001), TEX14 (P=0.008), TEX15 (P=0.009), ODF4 (P=0.008), AKAP4 (P=0.006), ACRBP P<0.001), PAGE4 (P<0.001), MAGEA4 (P=0.013), BORIS (P=0.024) and TSGA10 (P=0.021) – showed significantly increased expression. In contrast, expression of CTA was significantly decreased in tumor samples compared to normal tissue (p<0.001). In the bladder cancer specimens analyzed, expression of the CTA studied was significantly less than in the tumoradjacent control samples (P<0.001) Conclusions: CTA are expressed in urologic malignancies. Expression levels vary and may depend on tumor type. Our results showed mostly decreased expression of examined CTA in human bladder cancer tissues which may help cancer cells to avoid detection by immune competent cells and escape immune surveillance. Use of hypomethylating agents, which have been shown to increase the expression of CTA in various tumors, may have therapeutic value in these patients. Robust expression of these highly immunogenic genes in kidney cancer tissue may be used to design targeted vaccine therapies with possible tailoring to the individual patient depending on expression of a particular gene.
