A comparison of ARMS and direct sequencing for EGFR mutation analysis and tyrosine kinase inhibitors treatment prediction in body fluid samples of non-small-cell lung cancer patients.
A comparison of ARMS and direct sequencing for EGFR mutation analysis and tyrosine kinase inhibitors treatment prediction in body fluid samples of non-small-cell lung cancer patients.
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DOI：
10.1186/1756-9966-30-111
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发表时间：
2011-12-06
期刊：
影响因子：
--
通讯作者：
Liu XQ
中科院分区：
文献类型：
--
作者：
Liu Y;Liu B;Li XY;Li JJ;Qin HF;Tang CH;Guo WF;Hu HX;Li S;Chen CJ;Liu B;Gao HJ;Liu XQ
表皮生长因子受体(EGFR)突变与酪氨酸激酶抑制剂(TKIs)治疗非小细胞肺癌(NSCLC)的疗效密切相关。然而，突变分析所需的肿瘤组织通常是无法获得的。体液被认为是一种可行的分析替代方法，但临床实践中出现的突变率相对较低、临床相关性较差等问题尚未完全解决。在这项研究中，从220名患者中选择了50名有TKIS治疗经验和直接测序结果的患者(32名胸水和18名血浆)进行进一步分析。应用扩增难治突变系统(ARMS)对EGFR基因突变状态进行再评估，并对TKIs的临床结果进行回顾性分析。与直接测序法比较，16例阳性患者和23例阴性患者经ARM证实，其余11例阴性患者(6例胸水和5例血浆)重新定义为阳性，临床结果较好(PR 7例，SD 3例，PD 1例)。阳性患者的客观有效率(ORR)显著，胸水81.3%(直接测序法)和72.7%(ARMS)，血浆80%(ARMS)。值得注意的是，即使按ARM重新分类，阴性患者的ORR仍然相对较高，胸水和血浆的ORR分别为60%和46.2%。在使用体液进行EGFR突变分析时，无论采用何种方法，阳性结果始终是TKIs治疗的良好指标，其预测效果不亚于肿瘤组织。然而，即使按ARMS重新分类，TKIs的阴性结果与临床结果之间的相关性仍然不令人满意。结果表明，假阴性突变仍然存在，可通过采用对单个DNA分子敏感的方法或通过优化RNA或CTC的提取程序来解决，以确保检测到足够的肿瘤来源核酸。
Epidermal growth factor receptor (EGFR) mutation is strongly associated with the therapeutic effect of tyrosine kinase inhibitors (TKIs) in patients with non-small-cell lung cancer (NSCLC). Nevertheless, tumor tissue that needed for mutation analysis is frequently unavailable. Body fluid was considered to be a feasible substitute for the analysis, but arising problems in clinical practice such as relatively lower mutation rate and poor clinical correlation are not yet fully resolved. In this study, 50 patients (32 pleural fluids and 18 plasmas) with TKIs therapy experience and with direct sequencing results were selected from 220 patients for further analysis. The EGFR mutation status was re-evaluated by Amplification Refractory Mutation System (ARMS), and the clinical outcomes of TKIs were analyzed retrospectively. As compared with direct sequencing, 16 positive and 23 negative patients were confirmed by ARMS, and the other 11 former negative patients (6 pleural fluids and 5 plasmas) were redefined as positive, with a fairly well clinical outcome (7 PR, 3 SD, and 1 PD). The objective response rate (ORR) of positive patients was significant, 81.3% (direct sequencing) and 72.7% (ARMS) for pleural fluids, and 80% (ARMS) for plasma. Notably, even reclassified by ARMS, the ORR for negative patients was still relatively high, 60% for pleural fluids and 46.2% for plasma. When using body fluids for EGFR mutation analysis, positive result is consistently a good indicator for TKIs therapy, and the predictive effect was no less than that of tumor tissue, no matter what method was employed. However, even reclassified by ARMS, the correlation between negative results and clinical outcome of TKIs was still unsatisfied. The results indicated that false negative mutation still existed, which may be settled by using method with sensitivity to single DNA molecule or by optimizing the extraction procedure with RNA or CTC to ensure adequate amount of tumor-derived nucleic acid for the test.
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影响因子：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
通讯作者：
Haber, DA
评估血清 DNA 中表皮生长因子受体突变状态作为吉非替尼 (IRESSA) 反应的预测因子。
影响因子：
8.8
作者：
Kimura, H.;Suminoe, M.;Kasahara, K.;Sone, T.;Araya, T.;Tamori, S.;Koizumi, F.;Nishio, K.;Miyamoto, K.;Fujimura, M.;Nakao, S.
通讯作者：
Nakao, S.
影响因子：
51.1
作者：
Mitsudomi, Tetsuya;Morita, Satoshi;Fukuoka, Masahiro
通讯作者：
Fukuoka, Masahiro
影响因子：
45.3
作者：
Keedy, Vicki Leigh;Temin, Sarah;Giaccone, Giuseppe
通讯作者：
Giaccone, Giuseppe
影响因子：
158.5
作者：
Mok, Tony S.;Wu, Yi-Long;Fukuoka, Masahiro
通讯作者：
Fukuoka, Masahiro