EGFR-TKI明显提高EGFR突变型肺腺癌患者的总生存率，但约30%的EGFR突变型肺腺癌患者对EGFR-TKI的治疗原发耐药，目前普遍认为与KRAS等基因的突变有关，然而最新研究表明：肺腺癌对EGFR-TKI的原发耐药与上皮间质化（EMT）有关，在之前的研究中我们发现琥珀酸脱氢酶5（SDH5）蛋白能调节肺腺癌的EMT，不仅如此，在EGFR-TKI原发性耐药的肺腺癌患者中，也发现SDH5蛋白的表达明显下降，在细胞实验中，沉默SDH5的表达后，肺腺癌细胞对EGFR-TKI的敏感性明显下降，因此，我们推测SDH5通过EMT导致EGFR-TKI的原发性耐药,我们将通过Western blot、免疫沉淀等验证这一假设,该课题将进一步的阐明EGFR-TKI原发性耐药的作用机制，不仅如此，SDH5还可以作为EGFR-TKI治疗肺腺癌的评价指标，为精确EGFR-TKI的受益人群打下坚实的基础。

EGFR-TKI is a molecular target-therapeutic agent and it improve the survival rate of the lung adenocarcinoma patients with EGFR mutations,but a problem needed to be resolved that 30% lung adenocarcinoma patients with EGFR mutation remains primary drug-resistance to the therapy of EGFR-TKI. It is generally considered that EGFR-TKI primary drug resistance have relationship with KRAS mutation,The latest studies showed that the phenomenon of EMT correlated to EGFR-TKI primary drug-resistance, our previous study revealed that SDH5 protein can regulate EMT in NSCLC,and also in our cellular experiments, knocking down the expression of SDH5 protein, we found the sensitivity of lung adenocarcinoma cells to EGFR-TKI decreased significantly. So in this project, we speculate that loss of SDH5 protein is the reason for failure of first time EGFR-TKI treatment. Western blot, Co-immunoprecipitation assay will be used. If the project be succeed, The mechanism of EGFR-TKI primary resistance will be solved, and also the study offers evidence on SDH5 as a predicting factor for EGFR-TKI treatment,it will provide a basis to accurate beneficiaries.