Background: Osimertinib is approved by Food and Drug Administration for patients with advanced non-small cell lung cancer carrying EGFR-T790M mutations. Osimertinib therapy was missed in many patients who were unable to perform biopsy due to occult lesion progression or weak body. In this study. We hope that some proteins associated with predicting EGFR-T790M resistance could be screened from the serum to provide help for clinical medication. The aim of this study is to explore the protein associated with EGFR-T790M drug resistance gene and provide help for clinical medication.
Methods: In this study, 36 patients with advanced lung adenocarcinoma treated by gefitinib were included. After the disease progression of the patients, biopsy was performed. 18 patients in the EGFR-T790M mutation group and 18 patients in the non-EGFR-T790M mutation group were detected by the ARMS method. Serum of patients with drug resistance was collected, and proteins related to EGFR-T790M resistance were screened by isotopic marker relative and absolute quantitative marker combined with two-dimensional liquid chromatography tandem mass spectrometry proteomics technology.
Results: Seventeen different proteins were screened out, including 6 up-regulated proteins and 11 down-regulated proteins associated with EGFR-T790M gene mutation, which were mainly involved in 31 biological processes, 7 cell components and 26 molecular functions. Twelve enrichment pathways were identified, among which the highest enrichment index was the coagulation cascade pathway.
Conclusions: Seventeen proteins associated with EGFR-T790M resistance were found, and proteins involved in the coagulation cascade pathway are expected to be biomarkers associated with predicting EGFR-T790M resistance mutations.
【中文题目：鉴定晚期肺腺癌EGFR-T790M耐药基因突变 候选生物标志物】 【中文摘要：背景与目的 奥希替尼（Osimertinib）是美国食品和药物管理局（Food and Drug Administration, FDA）批准用于携带表皮生长因子受体（epidermal growth factor receptor, EGFR）-T790M突变的晚期非小细胞肺癌（non-small cell lung cancer, NSCLC）患者的药物，用药前需行EGFR-T790M检测。不少患者因进展病灶隐匿或体弱无法进行组织活检错过Osimertinib治疗，本研究希望能从血清中筛查出预测EGFR-T790M耐药突变相关蛋白，为临床用药提供帮助。本研究旨在探索EGFR-T790M耐药基因相关蛋白，为临床用药提供帮助。方法 本研究纳入口服易瑞沙晚期肺腺癌患者36例，在疾病进展后行组织活检，使用ARMS方法检测出EGFR-T790M突变组患者18例，非EGFR-T790M突变组18例。收集耐药患者血清，采用同位素标记相对和绝对定量标记结合二维液相色谱串联质谱蛋白组学技术筛选与EGFR-T790M耐药相关蛋白。结果 筛出17种差异性蛋白，与EGFR-T790M基因突变相关上调蛋白6种，下调蛋白11种，主要参与31种生物过程，7种细胞组分，26种分子功能；反应途径中共鉴定出12种富集途径，其中富集指数最高的是凝血级联途径。结论 发现与EGFR-T790M耐药相关蛋白共17种，参与凝血级联途径蛋白有望成为预测EGFR-T790M耐药突变相关的生物标志物。】 【中文关键词：晚期肺腺癌；EGFR-T790M；蛋白组学；差异性蛋白】.
Keywords: Advanced lung adenocarcinoma; Differentail proteins; EGFR-T790M; Proteomics.