Abstract：
To reveal the correlation of dynamic serum tumor markers (STMs) and molecular features of epidermal growth factor receptor-mutated (EGFR-mutated) lung cancer during targeted therapy, we retrospectively reviewed 303 lung cancer patients who underwent dynamic STM tests [neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), carbohydrate antigen 153 (CA153), the soluble fragment of cytokeratin 19 (CYFRA21-1), and squamous cell carcinoma antigen (SCC)] and circulating tumor DNA (ctDNA) testing with a panel covering 168 genes. At baseline, patients with EGFR mutation trended to have abnormal CEA, abnormal CA153, and normal SCC levels. Additionally, patients with Thr790Met (T790M) mutation were more likely to have abnormal CEA levels than patients without T790M mutation. Among patients with secondary resistance to EGFR tyrosine kinase inhibitors (TKI), the dynamic STMs showed a descending trend in the responsive stage and a rising trend in the resistant stage. However, the changing slopes differed between T790M subgroup and the non-T790M subgroup in individual STMs. Our study demonstrated that the combination of baseline levels and variations of STMs (including the responsive stage and resistant stage) can be suggestive of secondary EGFR-T790M mutation [area under the curve (AUC) = 0.897] and that changing trends of STMs (within 8 weeks after initiating the TKI therapy) can be potential predictors for the clearance of EGFR ctDNA [AUC = 0.871]. In conclusion, dynamic monitoring STMs can help to predict the molecular features of EGFR-mutated lung cancer during targeted therapy.
摘要：
揭示表皮生长因子受体突变（EGFR突变）肺癌靶向治疗过程中血清肿瘤标志物（STMs）与分子特征的相关性。我们回顾性分析了303例接受动态STM试验的肺癌患者[神经元特异性烯醇化酶(NSE),癌胚抗原(CEA),糖类抗原125(CA125),糖类抗原153(CA153),细胞角蛋白19的可溶性片段（CYFRA21-1），和鳞状细胞癌抗原（SCC）]和循环肿瘤DNA（ctDNA）测试，其中包含168个基因。在基线,EGFR突变的患者有CEA异常的趋势，异常的CA153和正常的SCC水平。此外,有Thr790Met(T790M)突变的患者比无T790M突变的患者更有可能出现CEA异常水平.在EGFR酪氨酸激酶抑制剂（TKI）继发耐药的患者中，动态STMs在反应阶段呈下降趋势，在抗性阶段呈上升趋势。然而,T790M亚组和非T790M亚组在个体STM中的变化斜率不同。我们的研究表明，基线水平和STM变异(包括反应期和耐药期)的组合可以提示继发性EGFR-T790M突变[曲线下面积(AUC)=0.897]，并且STM的变化趋势(在开始TKI治疗后8周内)可能是[EGFR清除]AUt71DNA的预测因子。总之,动态监测STMs有助于预测靶向治疗过程中EGFR突变肺癌的分子特征。
