Luo Bin, Yun Xiang, Fan Rong, Lin Yong-Da, He Shu-Jia, Zhang Qing-Mei, Mo Fa-Rong, Chen Fang, Xiao Shao-Wen, Xie Xiao-Xun
Department of Histology & Embryology, School of Pre-clinical Medicine, First Affiliated Hospital, Guangxi Medical University Nanning 530021, Guangxi Zhuang Autonomous Region, China ; Central Laboratory of Pre-clinical Medicine, First Affiliated Hospital, Guangxi Medical University Nanning 530021, Guangxi Zhuang Autonomous Region, China.
Int J Clin Exp Pathol. 2013 Nov 15;6(12):2835-45. eCollection 2013.
Cancer testis (CT) antigens are attractive targets for cancer immunotherapy because their expression is restricted in normal germ line tissues but frequently detected in variety of tumors. OY-TES-1 is identified as a member of CT antigens. Current knowledge about OY-TES-1 expression in colorectal cancer (CRC) is solely based on mRNA analysis. None of previous researches has studied OY-TES-1 at protein level. In this study, OY-TES-1 polyclonal antibody was generated. The expression of OY-TES-1 mRNA and protein was detected by RT-PCR and immunohistochemistry in 60 CRC and paired adjacent non-tumor tissues, 24 colorectal adenoma and 3 normal colon tissues, respectively. Sera from 73 CRC patients were also tested for OY-TES-1 antibody by ELISA. Our results showed that the frequency of OY-TES-1 mRNA expression was statistically higher in CRC (73.3%, 44/60) than that in adjacent non-tumor tissue (55.0%, 33/60) and colorectal adenoma (45.8%, 11/24). For the first time, OY-TES-1 protein expression was found in (43.3%, 26/60) of CRC tissues, but absent in any of adjacent non-tumor and colorectal adenoma tissues. No OY-TES-1 expression was found in normal colon by either RT-PCR or immunohistochemistry. Furthermore, OY-TES-1 protein expression was correlated with tumor invasion stage (P=0.004) and histological grade (P=0.040). Anti-OY-TES-1 antibody was detected in (9.6%, 7/73) of CRC patients' sera but not in 76 healthy donors. This finding demonstrates that OY-TES-1 is frequently expressed in CRC and is able to induce humoral immune response spontaneously in CRC patients, suggesting that it might be a promising immunotherapy target for CRC.
癌睾丸(CT)抗原是癌症免疫治疗的有吸引力的靶点,因为它们的表达在正常生殖系组织中受到限制,但在多种肿瘤中经常被检测到。OY-TES-1被鉴定为CT抗原成员之一。目前关于OY-TES-1在结直肠癌(CRC)中表达的知识仅基于mRNA分析。以前的研究均未在蛋白质水平上研究过OY-TES-1。在本研究中,制备了OY-TES-1多克隆抗体。分别通过RT-PCR和免疫组织化学检测了60例CRC及其配对的相邻非肿瘤组织、24例大肠腺瘤和3例正常结肠组织中OY-TES-1 mRNA和蛋白的表达。还通过ELISA检测了73例CRC患者血清中的OY-TES-1抗体。我们的结果显示,CRC中OY-TES-1 mRNA表达频率(73.3%,44/60)在统计学上高于相邻非肿瘤组织(55.0%,33/60)和大肠腺瘤(45.8%,11/24)。首次在43.3%(26/60)的CRC组织中发现了OY-TES-1蛋白表达,但在任何相邻非肿瘤组织和大肠腺瘤组织中均未发现。通过RT-PCR或免疫组织化学在正常结肠中均未发现OY-TES-1表达。此外,OY-TES-1蛋白表达与肿瘤浸润分期(P=0.004)和组织学分级(P=0.040)相关。在9.6%(7/73)的CRC患者血清中检测到了抗OY-TES-1抗体,但在76名健康供者中未检测到。这一发现表明OY-TES-1在CRC中频繁表达,并且能够在CRC患者中自发诱导体液免疫反应,提示它可能是CRC有前景的免疫治疗靶点。