肺癌已成为我国发病率及死亡率排名第一位的恶性肿瘤，EGFR-TKI靶向治疗成为目前新的治疗选择热点，但其疗效与患者个体化差异密切相关；筛选可能受益人群将会显著改善此类患者的生存，因此探索更加敏感或有补充作用的分子标志物用来指导临床EGFR-TKI用药尤为迫切。我们通过前期完成的非小细胞肺癌全基因组扫描及其他相关研究，发现了EGFR的可变剪接和由此造成的EGFR自身磷酸化，据此我们将在比较现有EGFR-TKI药物敏感性研究基础上，利用克隆的5个可变剪接进行EGFR-TKI耐药等研究，探索EGFR磷酸化蛋白是否更有效地可用于EGFR-TKI药物敏感性和耐药性的判定；同时构建这些标志物阳性和阴性的随访研究队列，开展为期2年的双盲病例随访研究，并进一步利用SCID免疫缺陷鼠移植瘤模型进行EGFR-TKI药物敏感性和耐药性的验证，以期为临床治疗中EGFR-TKI疗效预测与耐药监测提供一个新的思路。

Lung cancer has become the first morbidity and mortality of carcinoma in our country. Being a new treatment option in the clinical choice, EGFR-TKI targeted therapy is a hot spot in the research area. However, the efficacy is closely related to the individual difference in NSCLC (non small cell lung cancer) patients. Screening the population who may be benefit from EGFR-TKI drug will significantly improve the survival. So it is crucial to find the more sensitive molecular markers in the clinical EGFR-TKI theraphy. Our previous study found that the EGFR possessed the phosphorylation from the alternative splicing by the Genome-wide Scan method. Therefore, we will first compare the sensitivity with the current study of EGFR-TKI, and then use the five cloned alternative splicing for the EGFR-TKI resistant research to determine if the EGFR phosphorylation protein is more effective and sensitivity to EGFR-TKI choice. A double-blind follow-up cohort study divided by these positive and negative markers will be performed during in the two years, and then the SCID EGFR-TKI immunodeficient mice model which was transplanted by lung cancer tissue will be used to verify the sensitivity and resistance of EGFR-TKI drug. All the results will help to provide a new idea for the drug prediction and resistance surveillance of the EGFR-TKI clinical treatment.