Division of Surgery, University of Nottingham, Nottingham, United Kingdom.
Clin Cancer Res. 2011 Mar 15;17(6):1474-80. doi: 10.1158/1078-0432.CCR-10-1363. Epub 2010 Dec 7.
We investigated the presence of autoantibodies as immunobiomarkers to a panel of tumor-associated antigens in a group of individuals with small cell lung cancer (SCLC), a disease group that has a poor overall cancer prognosis and therefore may benefit most from early diagnosis.
Sera from 243 patients with confirmed SCLC and normal controls matched for age, sex, and smoking history were analyzed for the presence of these early immunobiomarkers (i.e., autoantibodies to p53, CAGE, NY-ESO-1, GBU4-5, Annexin I, SOX2, and Hu-D) by ELISA.
Autoantibodies were seen to at least 1 of 6 antigens in 55% of all the SCLC patients' sera tested, with a specificity of 90% compared with controls. Using a higher assay cutoff to achieve a specificity of 99%, autoantibodies were still detectable in 42% of SCLC patients (receiver operator characteristic area under the curve = 0.76). There was no significant difference in sensitivity when analyzed by stage of the cancer or by patient age or gender. The frequency of autoantibodies to individual antigens varied, ranging from 4% for GBU4-5 to 35% for SOX2. Levels of Annexin I autoantibodies were not elevated in patients with SCLC. Antibodies were also detected in 4 separate patients whose sera were taken up to 3 months before tumor diagnosis.
The presence of an autoantibody to one or more cancer-associated antigens may provide an important addition to the armamentarium available to the clinician to aid early detection of SCLC in high-risk individuals.
我们研究了一组小细胞肺癌（SCLC）患者中肿瘤相关抗原的自身抗体作为免疫生物标志物的存在情况。该疾病患者总体癌症预后较差，因此可能最受益于早期诊断。
通过 ELISA 分析了 243 例确诊为 SCLC 的患者和年龄、性别和吸烟史相匹配的正常对照者的血清中这些早期免疫生物标志物（即 p53、CAGE、NY-ESO-1、GBU4-5、 Annexin I、SOX2 和 Hu-D 的自身抗体）的存在情况。
在所有检测的 SCLC 患者血清中，有 55%的患者至少对 6 种抗原中的 1 种产生了自身抗体，与对照组相比特异性为 90%。使用更高的检测截止值以达到 99%的特异性，仍然可以在 42%的 SCLC 患者中检测到自身抗体（受试者工作特征曲线下面积为 0.76）。按癌症分期、患者年龄或性别分析，敏感性没有显著差异。针对单个抗原的自身抗体的频率不同，从 GBU4-5 的 4%到 SOX2 的 35%不等。SCLC 患者的 Annexin I 自身抗体水平没有升高。在 4 位患者的血清中也检测到了抗体，他们的血清是在肿瘤诊断前 3 个月采集的。
一种或多种癌症相关抗原的自身抗体的存在可能为临床医生提供重要的辅助手段，以帮助高危人群中早期检测 SCLC。
