Department of Pathology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Cancer Biomark. 2010;6(1):33-48. doi: 10.3233/CBM-2009-0117.
Biomarkers for early detection of cancer have great clinical diagnostic potential. Numerous reports have documented the generation of humoral immune responses that are triggered in response to changes in protein expression patterns in tumor tissues and these biomarkers are referred to as tumor associated antigens (TAAs). Using a high-throughput technology, we previously identified 65 proteins as diagnostically useful TAAs by profiling the humoral immune responses in ovarian cancer (OVCA) patients. Here we determined the expression status of some of those TAAs in tissues from OVCA patients. The protein expression patterns of 4 of those 65 antigens, namely NASP, RCAS1, Nijmegen breakage syndrome1 (NBS1) and eIF5A, along with p53 and Her2 (known molecular prognosticators) and two proteins that interact with NBS1, MRE11 and RAD50, were assessed by immunohistochemistry (IHC). NASP and RCAS1 proteins were more frequently expressed in ovarian cancer tissues than with normal ovarian tissue and serous cystadenomas and MRE11 was less frequently expressed. When evaluated simultaneously, only NASP and MRE11 remained statistically significant with sensitivity of 66% and specificity of 89%. None of these proteins' expression levels were prognostic for survival. Together, our results indicate that occurrence of humoral immune responses against some of these TAAs in OVCA patients is triggered by antigen protein overexpression.
用于癌症早期检测的生物标志物具有很大的临床诊断潜力。大量报告记录了体液免疫应答的产生，这些应答是针对肿瘤组织中蛋白质表达模式的变化而触发的，这些生物标志物被称为肿瘤相关抗原（TAA）。我们之前使用高通量技术，通过分析卵巢癌（OVCA）患者的体液免疫反应，鉴定了 65 种具有诊断意义的 TAA。在此，我们确定了其中一些 TAA 在 OVCA 患者组织中的表达状态。通过免疫组织化学（IHC）评估了其中 4 种 TAA 的蛋白表达模式，即 NASP、RCAS1、Nijmegen 断裂综合征 1（NBS1）和 eIF5A，以及 p53 和 Her2（已知的分子预后标志物）和与 NBS1 相互作用的两种蛋白质，即 MRE11 和 RAD50。NASP 和 RCAS1 蛋白在卵巢癌组织中的表达频率高于正常卵巢组织和浆液性囊腺瘤，而 MRE11 的表达频率较低。同时评估时，只有 NASP 和 MRE11 仍然具有统计学意义，敏感性为 66%，特异性为 89%。这些蛋白质的表达水平均与生存无关。总之，我们的结果表明，OVCA 患者中针对这些 TAA 中的一些发生体液免疫应答是由抗原蛋白过表达触发的。
