癌细胞存在数百个基因突变点，多个突变点之间活性的协同抑制是控制肿瘤的关键，所以基因水平上治疗个性化方案的调整对肺癌的疗效很重要。高通量测序肿瘤循环DNA（ctDNA）具有同时测定多片段、多位点、快捷高效的特点，对肿瘤检测的高度敏感性，可用于肿瘤的分子病理学诊断及个性化用药指导，已在最近的肝癌监测研究中显示出巨大的诊断潜力。质谱相关的蛋白组研究也具有同时测定百种肿瘤分子标志物的快捷高效的特点，不仅适合早期诊断，也适用于评估临床疗效及预后状况。最近建立的分离肺结节(SPN) 模型显示，支持向量机在确定SPN分化的程度及区分良性及恶性具有明显优势。本项目拟以肺癌临床血液与病理活检为样本，通过SPN及常规医疗分组疾病发展的不同阶段点，检测ctDNA水平，确定其对监测肺癌转移倾向及个性化治疗调节的价值；测定蛋白组标志物的质谱变化，确定肿瘤疗效及预后评估的高科技检测手段。

There might be hundreds of susceptibility mutations exist in a single cancer cell. The efficiency in synergistic inhibition of the activity among multiple mutation points is the key factor to guarantee the therapeutic effect of any inhibitor. Therefore, a personalized treatment is critical for curing lung cancer patients in clinic. Recently, high-throughput sequencing of circular tumor DNA (ctDNA) , which is convenient and efficient to test multi-genetic slices and multi-mutation points, have been used for molecular pathological diagnosis and individualized treatment. This technique has shown a great diagnosis potential for cancer with high sensitivity. Mass spectrometry (MALD-TOF- MS/MS) related proteomic study also have the ability in simultaneous testing of tens or even hundreds of cancer biomarker with high convenience and efficiency. This technique can be used not only for cancer early diagnosis, but also for evaluation of therapeutic effect and after the cure. In the study of Lewis lung cancer (LLC), our data suggested that TRPM8 induces UCP2 to trigger metabolic transformation, whereas TRPA1 induces autophagy during adverse conditions. The combination of both genes contributes directly to an invasive phenotype in lung carcinoma. Our other result also indicated the high relationship of accuracy, sensitivity and specificity of the support vector machine (SVM) diagnostic model, indicating the important reference value of the model for determining the degree of solitary pulmonary nodules (SPN) differentiation and is suitable for the auxiliary diagnosis of benign and malignant SPN. Under refined classification of the medical examination of SPNS and routine lab test, our project is designed to collect the samples of blood and pathological biopsy from lung cancer patients at different stages of tumor progress. Then the changes of biomarker level in serum will be traced and the value of clinical diagnostic potential for lung cancer development will be determined. Our research goal is to monitor the potential metastasis of lung cancer tendency and to establish the individualized treatment measures in order to provide practical monitoring system with advanced technology in clinic.