College of Life Sciences, Northwest University, Xi'an, 710069, China.
School of Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
Sci Rep. 2017 Aug 21;7(1):8346. doi: 10.1038/s41598-017-08210-8.
Epidermal growth factor receptor (EGFR) mutations predict better outcomes with EGFR tyrosine kinase inhibitors in patients with non-small cell lung cancer (NSCLC). Most common activating mutations include in-frame deletion in exon 19 and L858R substitution in exon 21, which account for >90% of all EGFR mutations in NSCLC. In this study, a PCR-GoldMag lateral flow assay (PCR-GoldMag LFA) was developed for the visual detection of delE746-A750 and L858R of EGFR mutations. Forty formalin-fixed paraffin-embedded (FFPE) tissue samples of NSCLC patients were analyzed using PCR-GoldMag LFA system and verified by direct sequencing and TaqMan-PCR detection methods. Results showed that EGFR mutations were detected in 34 cases among the 40 samples (85%) by PCR-GoldMag LFA method. Among the 34 cases, 5 cases were simultaneously detected with delE746-A750 in exon 19 and L858R mutation in exon 21. Compared with sequencing, only 4 samples were detected as delE746-A750, which revealed higher sensitivity of PCR-GoldMag LFA detection method than direct sequencing. TaqMan-PCR method verified the L858R mutation and was in 100% agreement with our method. These results indicated that our method has obvious advantages to analyze clinical samples and offers a more sensitive alternative to direct sequencing for the detection of EGFR mutations.
表皮生长因子受体 (EGFR) 突变预测非小细胞肺癌 (NSCLC) 患者使用 EGFR 酪氨酸激酶抑制剂的效果更好。最常见的激活突变包括外显子 19 的框内缺失和外显子 21 的 L858R 取代,这占 NSCLC 中所有 EGFR 突变的>90%。在这项研究中,开发了一种用于 EGFR 突变的德尔 E746-A750 和 L858R 可视化检测的 PCR-GoldMag 侧流分析 (PCR-GoldMag LFA)。使用 PCR-GoldMag LFA 系统分析了 40 例 NSCLC 患者的福尔马林固定石蜡包埋 (FFPE) 组织样本,并通过直接测序和 TaqMan-PCR 检测方法进行了验证。结果表明,PCR-GoldMag LFA 方法在 40 个样本中的 34 个样本 (85%) 中检测到 EGFR 突变。在 34 例中,5 例同时在外显子 19 中检测到德尔 E746-A750 与外显子 21 中的 L858R 突变。与测序相比,仅检测到 4 个样本为德尔 E746-A750,这表明 PCR-GoldMag LFA 检测方法的灵敏度高于直接测序。TaqMan-PCR 方法验证了 L858R 突变,与我们的方法完全一致。这些结果表明,我们的方法在分析临床样本方面具有明显优势,为 EGFR 突变的检测提供了一种比直接测序更敏感的替代方法。