慢性炎症与肺癌发生发展密切相关。C反应蛋白(CRP)是炎症反应标志物，血清CRP浓度升高是肺癌的高危因素，但其浓度受多因素影响，用于肺癌早期诊断特异性不高。CRP通过与配体(如凋亡或坏死细胞降解产物) 结合形成CRP复合物，激活补体和单核吞噬细胞系统，清除废物。我们发现肺癌患者血清CRP复合物中存在CK7、CEACAM5、SAA1等与肿瘤相关的分子，而肺炎和正常人血清CRP复合物中则未检测到。这提示肺癌患者血清CRP复合物中存在特异标志物。但目前CRP结合的配体作为肺癌标志物尚无相关报道。本课题拟：①采用靶向CRP复合物的"鸟枪法"定量蛋白质组技术，在前期工作基础上进一步从CRP复合物中筛选出肺癌早期诊断特异标志物；②建立夹心ELISA技术检测筛选的标志物；③大规模临床验证其在肺癌早期诊断和疗效判断的价值。本课题研究将发现新的肺癌特异标志物并建立检测试剂盒，用于肺癌的早期诊断及疗效判断。

Chronic inflammation has been recognized to play a very important role in lung carcinogenesis. C-reaction protein (CRP) is a sensitive marker and mediator of inflammation. The epidemiologic studies indicate that the increased level of circulating CRP is a high risk factor for lung cancer. However, CRP is not a specific biomarker for lung cancer because many factors could affect its serum level. CRP can bind to exogenous and endogenous ligands and results in CRP complexes which regulate the immune function of phagocytic cell. We found that some tumor progression associated molecules, such as CK7、CEACAM5、SAA1 could be detected in serum CRP complexes from patients with lung cancer, while remain undetectable in serum CRP complexes from healthy donors and patients with pneumonia. These results suggested that some specific biomarkers for lung cancer might exist in the circulating CRP complexes. No similar research has been reported. To find more specific and suitable biomarkers for lung cancer, we plan to develop the following researches: (1) We will perform a target proteomic study of circulating CRP complexes using bead-based immunopurification and shotgun proteomics by2D- LC/MS/MS. We would not only identify new tumor markers in serum CRP complexes, but also confirm our previous study by this method. （2）A sandwich ELISA assay will be established to detect the candidates of biomarkers. (3) A large scale of clinical validation of these biomarkers will be carried out to evaluate their clinical values in early diagnosis or prognosis prediction for lung cancer. This study will indentify new specific biomarkers for lung cancer and establish sensitive ELISA test kits, which could be employed in the early diagnosis and prognosis prediction of lung cancer, and provide a novel strategy for prevention and treatment of lung cancer.