Analysis Of Mutation Of Plasma Free DNA EGFR Gene And Its Correlation With EGFR - TKI Effect By DdPCR Method

Objective:Our study aims to determine the feasibility of using ddPCR to detect plasma EGFR mutations in NSCLC patients, explore the factors influencing the sensitivity of the method, and establish a correlation between plasma EGFR mutation and EGFR-tyrosine kinase inhibitor (TKI) efficacy.Methods:215 plasma and tumor tissue specimens were obtained. ddPCR was used to detect the common sensitive EGFR gene mutations in plasma, and the EGFR mutations of tissue specimens had been detected with the amplification refractory mutation system(ARMS) before.Results:61 sensitive Exon21 L858R and Exon19 del mutations (61/215,28.4%) were found by ddPCR. Compared with tumor tissue-based EGFR gene detection, the sensitivity of ddPCR in the detection of plasma gene mutations was 61.3%, the specificity was 96.7%, and the consistency rate was 81.4%(k= 0.605,95%CI,0.501-0.706, P< 0.0001). There were significantly higher mutation rates in the never-smokers and in the stageⅥ. The DNA copy number of patients who tested positive in plasma was higher than that of those who tested negative (1570 vs.511, P< 0.001,95%CI,0.000-0.032). Plasma mutation-positive patients treated with EGFR-TKIs showed longer progression-free survival time than the negative, but no statistical difference was observed between these patients(334 vs 181,P= 0.123).Conclusions:ddPCR has a high sensitivity in detecting plasma mutations. The sensitivity of ddPCR in detecting plasma EGFR mutations is related with the DNA copy number.