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血清中 EGFR 和 KRAS 的突变能否成为晚期非小细胞肺癌(NSCLC)患者的预测和预后标志物?

Can mutations of EGFR and KRAS in serum be predictive and prognostic markers in patients with advanced non-small cell lung cancer (NSCLC)?

机构信息

Division of Hematology-Oncology, Department of Medicine, Korea University Anam Hospital, Korea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul 136-705, South Korea.

出版信息

Med Oncol. 2013 Mar;30(1):328. doi: 10.1007/s12032-012-0328-3. Epub 2013 Jan 10.

DOI:10.1007/s12032-012-0328-3
PMID:23307237
Abstract

The status of epidermal growth factor receptor (EGFR) and Kirsten ras (KRAS) mutations has been used widely in management of patients with non-small cell lung cancer (NSCLC). However, it may be difficult to get tumor tissues for analyzing the status of EGFR and KRAS mutation in large proportion of patients with advanced disease. We obtained pairs of tumor and serum samples from 57 patients with advanced NSCLC, between March 2006 and January 2009. EGFR mutation status from tumor samples and KRAS mutation status from serum samples were analyzed by genomic polymerase chain reaction and direct sequence, and EGFR mutation status from serum samples was determined by the peptide nucleic acid-locked nucleic acid PCR clamp. EGFR mutations were detected in the serum samples of 11 patients and in the tumor samples of 12 patients. Fourteen patients revealed (?) KRAS mutation in the serum sample. EGFR mutation status in the serum and tumor samples was consistent in 50 (87.7 %) of the 57 pairs (correlation index 0.62, p < 0.001). Only 5 of 57 (8.7 %) patients showed mutation of both EGFR and KRAS in serum sample. Twenty-two of 57 patients (38.5 %) received EGFR-TKIs as any line therapy. The response for EGFR-TKIs was significantly associated with EGFR mutations in both tumor samples and serum samples (p < 0.05). The status of KRAS mutation in serum was not predictive for the response of EGFR-TKI (p > 0.05). There was no significant difference in OS according to the status of EGFR mutations in both serum and tumor samples (p > 0.05) and KRAS mutations in serum samples (p > 0.05). The status of EGFR and KRAS mutation in serum was not prognostic in patients with advanced NSCLC. However, the clinical usefulness of EGFR mutation of serum as a selection marker for EGFR-TKIs sensitivity in NSCLC might be allowed, not KRAS mutation.

摘要

表皮生长因子受体 (EGFR) 和 Kirsten 鼠肉瘤病毒 (KRAS) 突变状态已广泛用于非小细胞肺癌 (NSCLC) 患者的治疗。然而,对于大多数晚期疾病患者,获得肿瘤组织来分析 EGFR 和 KRAS 突变状态可能很困难。我们从 2006 年 3 月至 2009 年 1 月期间的 57 名晚期 NSCLC 患者中获得了肿瘤和血清样本对。通过基因组聚合酶链反应和直接测序分析肿瘤样本中的 EGFR 突变状态和血清样本中的 KRAS 突变状态,并通过肽核酸-锁核酸 PCR 夹测定血清样本中的 EGFR 突变状态。在 11 名患者的血清样本和 12 名患者的肿瘤样本中检测到 EGFR 突变。在 14 名患者的血清样本中发现 KRAS 突变。在 57 对样本中,有 50 对(87.7%)血清和肿瘤样本中的 EGFR 突变状态一致(相关指数 0.62,p < 0.001)。在 57 名患者中,只有 5 名患者在血清样本中同时存在 EGFR 和 KRAS 突变。57 名患者中有 22 名(38.5%)接受了任何一线治疗的 EGFR-TKIs。EGFR-TKIs 的反应与肿瘤样本和血清样本中的 EGFR 突变均显著相关(p < 0.05)。血清 KRAS 突变状态对 EGFR-TKI 的反应没有预测作用(p > 0.05)。根据血清中 EGFR 突变状态和肿瘤样本中 KRAS 突变状态的不同,OS 无显著差异(p > 0.05)。在晚期 NSCLC 患者中,血清中 EGFR 和 KRAS 突变状态无预后意义。然而,血清中 EGFR 突变作为 NSCLC 患者对 EGFR-TKIs 敏感性的选择标志物的临床应用可能是允许的,而 KRAS 突变则不然。

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本文引用的文献

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J Clin Oncol. 2011 Nov 1;29(31):4113-20. doi: 10.1200/JCO.2010.31.8162. Epub 2011 Oct 3.
2
Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study.厄洛替尼对比化疗用于治疗晚期 EGFR 突变阳性非小细胞肺癌患者的一线治疗(OPTIMAL、CTONG-0802):一项多中心、开放标签、随机、III 期研究。
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将基于血液的液体活检信息纳入癌症分期:是时候采用 TNMB 系统了吗?
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Prognostic value of EGFR and KRAS in circulating tumor DNA in patients with advanced non-small cell lung cancer: a systematic review and meta-analysis.表皮生长因子受体(EGFR)和 Kirsten 大鼠肉瘤病毒癌基因(KRAS)在晚期非小细胞肺癌患者循环肿瘤 DNA 中的预后价值:一项系统评价和荟萃分析。
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