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Quantification of epidermal growth factor receptor (EGFR) mutation may be a predictor of EGFR‐tyrosine kinase inhibitor treatment response

机译:表皮生长因子受体(EGFR)突变的量化可能是EGFR-酪氨酸激酶抑制剂治疗反应的预测指标

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BackgroundEpidermal growth factor receptor (EGFR) gene mutation is a reliable predictive factor for response to EGFR-tyrosine kinase inhibitors (TKIs). The quantified EGFR value may also predict response and survival within an EGFR mutated group. MethodsWe conducted a retrospective study of 836 lung cancer patients. The patient sample was divided into two groups based on the mean delta cycle threshold (?Ct) value. EGFR mutation tests using peptide nucleic acid (PNA)-mediated clamping polymerase chain reaction (PCR) were performed. The efficiency of PCR clamping was determined by measuring the Ct value and EGFR quantification was determined by the corrected ?Ct value. Results EGFR mutation positivity was 30.1% and there were 235 single activating mutations. In this mutation group, the higher corrected ?Ct value (≥ mean value) group showed better objective response (70.9% vs. 54.9%, P =?0.022) and clinical benefit rates (86.4% vs. 68.3%, P =?0.003) than the lower group. In addition, corrected ?Ct values were significantly and inversely correlated with disease response ( r =??0.184, P =?0.017). In multivariate analysis, both female gender ( P =?0.014) and higher corrected ΔCt value ( P =?0.012) were independent predictive factors for better clinical benefit rate. The higher corrected ΔCt value group had a tendency for longer progression-free survival than the lower group ( P =?0.050). ConclusionThe corrected ?Ct value, which refers to EGFR quantification by PNA-mediated PCR clamping, can predict better clinical response to EGFR-TKI therapy. However, further study is warranted to determine its value as a biomarker to reflect survival.
机译:背景表皮生长因子受体(EGFR)基因突变是对EGFR酪氨酸激酶抑制剂(TKIs)反应的可靠预测因子。量化的EGFR值还可以预测EGFR突变组内的应答和存活。方法我们对836例肺癌患者进行了回顾性研究。根据平均delta循环阈值(ΔCt)值将患者样本分为两组。使用肽核酸(PNA)介导的钳位聚合酶链反应(PCR)进行了EGFR突变测试。通过测量Ct值确定PCR钳制的效率,并通过校正后的ΔCt值确定EGFR定量。结果EGFR突变阳性率为30.1%,单激活突变为235个。在该突变组中,较高的校正后的?Ct值(≥平均值)组显示出更好的客观反应(70.9%对54.9%,P =?0.022)和临床受益率(86.4%对68.3%,P =?0.003)。 )的排名低于下组。另外,校正后的ΔCt值与疾病反应显着负相关(r =≤0.184,P =≤0.017)。在多变量分析中,女性(P =?0.014)和较高的校正ΔCt值(P =?0.012)都是提高临床受益率的独立预测因素。较高的校正ΔCt值组比较低的组有更长的无进展生存期趋势(P =?0.050)。结论校正后的?Ct值,即通过PNA介导的PCR钳制对EGFR定量,可以预测对EGFR-TKI治疗的更好的临床反应。但是,有必要进一步研究确定其作为反映生存的生物标志物的价值。

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