Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology, Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing, China.
Clin Cancer Res. 2010 Feb 15;16(4):1324-30. doi: 10.1158/1078-0432.CCR-09-2672. Epub 2010 Feb 9.
Non-small cell lung cancer (NSCLC) with KRAS mutation may be resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). This study aims to evaluate a plasma-based KRAS mutation analysis and the clinical significance of plasma KRAS mutation as a predictive marker for tumor resistance to EGFR-TKIs in patients with NSCLC.
DNA extracted from plasma and matched tumor tissues were obtained from 273 patients with advanced stage NSCLC. Patients were followed up prospectively for treatment outcomes. KRAS mutations in codon 12 and 13 were detected using PCR-restriction fragment length polymorphism. Mutations in plasma and matched tumors were compared. Associations between KRAS mutation status and patients' clinical outcomes were analyzed.
KRAS mutation was found in 35 (12.8%) plasma samples and 30 (11.0%) matched tumor tissues. The consistency of KRAS mutations between plasma and tumors is 76.7% (23 of 30; kappa = 0.668; P < 0.001). Among 120 patients who received EGFR-TKI treatment, the response rate was only 5.3% (1 of 19) for patients with plasma KRAS mutation compared with 29.7% for patients with no KRAS mutation in plasma DNA (P = 0.024). The median progression-free survival time of patients with plasma KRAS mutation was 2.5 months compared with 8.8 months for patients with wild-type KRAS (P < 0.001).
KRAS mutation in plasma DNA correlates with the mutation status in the matched tumor tissues of patients with NSCLC. Plasma KRAS mutation status is associated with a poor tumor response to EGFR-TKIs in NSCLC patients and may be used as a predictive marker in selecting patients for such treatment.
KRAS 基因突变的非小细胞肺癌（NSCLC）可能对表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）产生耐药性。本研究旨在评估基于血浆的 KRAS 突变分析以及血浆 KRAS 突变作为预测 NSCLC 患者肿瘤对 EGFR-TKI 耐药的标志物的临床意义。
从 273 名晚期 NSCLC 患者的血浆和配对肿瘤组织中提取 DNA。对患者进行前瞻性随访以评估治疗结果。采用 PCR-限制性片段长度多态性检测 12 和 13 密码子的 KRAS 突变。比较血浆和配对肿瘤中的突变。分析 KRAS 突变状态与患者临床结局之间的关系。
在 35 份（12.8%）血浆样本和 30 份（11.0%）配对肿瘤组织中发现 KRAS 突变。血浆和肿瘤之间 KRAS 突变的一致性为 76.7%（23/30；kappa = 0.668；P < 0.001）。在接受 EGFR-TKI 治疗的 120 名患者中，血浆 KRAS 突变患者的反应率仅为 5.3%（1/19），而血浆 DNA 中无 KRAS 突变的患者为 29.7%（P = 0.024）。血浆 KRAS 突变患者的中位无进展生存期为 2.5 个月，而 KRAS 野生型患者为 8.8 个月（P < 0.001）。
血浆 DNA 中的 KRAS 突变与 NSCLC 患者配对肿瘤组织中的突变状态相关。血浆 KRAS 突变状态与 NSCLC 患者对 EGFR-TKI 的肿瘤反应不良相关，可作为选择此类治疗患者的预测标志物。
