非小细胞肺癌（NSCLC）EGFR-TKI获得性耐药的机制及临床应对策略已是目前靶向治疗领域急待解决的问题。课题组认为编码基因遗传学水平异常在EGFR-TKI耐药中的影响权重较低，而miRNA作为表观遗传学调控的重要机制则与之密切相关。课题组已初步发现一组血浆miRNA差异表达谱（miR-21、miR-210、miR-125b、miR-27a、miR-200c；miR-22、 miR-497、miR-203）与NSCLC厄洛替尼获得性耐药密切相关，我们拟进一步扩大临床样本检测明确耐药相关血浆miRNA标志物，同时从对上述miRNA具有一定共同调控作用的转录因子（c-Fos、TCF12、STAT3、EGR1）和启动子甲基化两个角度，运用耐药细胞和体内实验，研究其差异表达的上游调控机制和体内外调控耐药的功能和相关信号通路，为EGFR-TKI获得性耐药的动态监测、早期评判和机制完善提供重要信息。

The mechanism of Non-small cell lung cancer(NSCLC) EGFR-TKI acquired resistance and the clinical response strategy against it have become a research hotspot in the field of molecular targeted therapy. Many research inspired us that genetic abnormalities of encoding genes might play a weak role in the EGFR-TKI resistance while epigenetic alternation, such as miRNA regulation, might be widely involved. We have found a group of plasma miRNAs (miR-21, miR-210, miR-125b, miR-27a, miR-200c; miR-22, miR-497, miR-203 ) are closely related with erlotinib acquired drug resistance in non small cell lung cancer patients and we intend to expand clinical samples to verify it; meanwhile, we will study the mechanism of the differential expression level of above miRNAs by transcription factors with some co-regulatory role such as c-Fos, TCF12, STAT3, EGR1 or methylation in miRNA promoters using drug resistant cell line then combining with in vivo experiment model finally elucidate the regulation mechanism of the functional plasma miRNA biomarker which is not only predictive for erlotinib acquired resistance but also modulating it. Our research will provide more information for monitoring and early detection of EGFR-TKI acquired drug resistance in NSCLC patients.