自身抗体图谱在预测吸烟人群中非小细胞肺癌风险的研究

Cigarette smoking is the number one cause of lung cancer. It is critical and difficult to identify those individuals who have high susceptibilities to lung cancer from high-risk smoking populations. In this study, we will take the advantage of immune surveillance to identify smoking-related non-small cell lung cancer (NSCLC) autoantibody profiles using phage-display and protein microarray technologies by screening a large number of banked serum samples from non-smoking normal, smoking normal and smoking NSCLC populations. In previous studies, we successfully identified 5 autoantibody biomarkers for the detection of early stage NSCLC with both sensitivity and specificity of 91.3%. However, the same autoantibody biomarkers could not accurately predict the potential risks of NSCLC from high-risk smoking populations in the preliminary study. Therefore, in this study we will extend our previous study to identifying smoking-related NSCLC autoantibody profiles as biomarkers. Eventually, the combined autoantibody profiles will be used as a screening test for predicting the risk of NSCLC, as well as for detecting the early stage NSCLC from high-risk smoking populations.

吸烟是导致肺癌的首要危险因素，如何能从高风险的吸烟人群中准确地识别出肺癌的"易感人群"已成为临床上亟待解决的难题。因此，本项目根据免疫监视原理，运用噬菌体展示与蛋白芯片技术相结合，利用大量已存的非吸烟正常人群、吸烟正常人群和吸烟型非小细胞肺癌(NSCLC)患者血清样本及随访记录，进行生物淘洗、芯片筛选和统计分析，从而得到与吸烟型NSCLC相关的自身抗体图谱。运用此类方法，申请人已在前期工作中成功筛选到了5种NSCLC早期诊断自身抗体，其联合诊断的敏感性及特异性均达到91.3%。虽然在预试验中这5中抗体展示出了一定的区分吸烟型NSCLC的能力，但其尚不能够对随访的吸烟人群中NSCLC进行准确预测。因此，本项目将结合前期的工作基础，将吸烟与NSCLC风险预测结合起来，筛选出高敏感性和特异性的自身抗体图谱，用于高风险吸烟人群中NSCLC发病的筛查及早期诊断，从而降低NSCLC的发病率及死亡率。

吸烟是导致肺癌的首要危险因素，肺癌患者中90%为吸烟人群。由于吸烟诱发肺癌产生要经历10年多的时间，如何能从高危的吸烟人群中准确地识别出肺癌的“易感人群”已为成为临床上亟待解决的难题。因此，本项目根据免疫监视原理，运用噬菌体展示与蛋白芯片技术相结合，利用大量已存的不吸烟正常人群、吸烟正常人群和吸烟型非小细胞肺癌(NSCLC)患者血清样本及随访记录，进行生物淘洗和统计分析，从而筛选出6个与吸烟和肺癌相关的特异性抗原（BMI1, GAGE7, LTBP1, CAGE, Annexin1, SOX2）。通过对200份吸烟正常人群和吸烟肺癌人群的血清中相对应的自身免疫抗体进行双盲法验证，准确的从100位吸烟肺癌病人中预测出83位癌症患者（敏感性83%），而正确的从100位吸烟正常人群中鉴别出78位正常烟民（特异性78%）。目前这一检测方法包括肿瘤标志物蛋白正在申报国家专利，为今后临床上预测吸烟诱发肺癌提供了一种新方法。为了进一步提高检测的准确性，课题组还对NSCLC血清中DNA甲基化、白细胞端粒长度在诊断及预后中的应用进行了研究。研究发现RUNX3、RASSF1A、3-OST2、DAPK、PTPRO基因甲基化检出率明显高于正常人，联合检测可能有助于NSCLC早期诊断及其预后评估。