Comparative Analysis of Two Methods for the Detection of EGFR Mutations in Plasma Circulating Tumor DNA from Lung Adenocarcinoma Patients

Cancers

Jr-Hau Lung¹  Shu-Yi Huang²  Yu-Hung Fang²  Yuan-Yuan Jiang²  Ming-Szu Hung²  Yu-Ching Lin²  Meng-Jer Hsieh²  Ying-Huang Tsai³ 

[1] Department of Medical Research, Chang Gung Memorial Hospital, Chiayi branch 61363, Taiwan;Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi branch 61363, Taiwan;Department of Respiratory Care, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan;

关键词: lung cancer;    EGFR;    TKI;    ctDNA;    ARMS;    MassARRAY;   

DOI  :  10.3390/cancers11060803

来源: DOAJ

【 摘 要 】

Mutations in the epidermal growth factor receptor (EGFR) are associated with various solid tumors. This study aimed to compare two methods for the detection of EGFR mutations in circulating tumor DNA (ctDNA) from lung adenocarcinoma (LUAD) patients and to evaluate the clinical significance of EGFR mutations in ctDNA. In this prospective cohort study, the EGFR mutation status of 77 patients with stage IIIB or IV LUAD was first determined using lung cancer tissue. The amplification refractory mutation system (ARMS) and single allele base extension reaction combined with mass spectroscopy (SABER/MassARRAY) methods were also used to detect EGFR mutations in plasma ctDNA from these patients and then compared using the EGFR mutation status in lung cancer tissue as a standard. Furthermore, the relationship between the presence of EGFR mutations in ctDNA after receiving first-line EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy and survival was evaluated. The overall sensitivity and specificity for the detection of EGFR mutations in plasma ctDNA by ARMS and SABER/MassARRAY were 49.1% vs. 56% and 90% vs. 95%, respectively. The agreement level between these methods was very high, with a kappa-value of 0.88 (95% CI 0.77−0.99). Moreover, 43 of the patients who carried EGFR mutations also received first-line EGFR-TKI therapy. Notably, patients with EGFR mutations in plasma ctDNA had significantly shorter progression-free survival (9.0 months, 95% CI 7.0−11.8, vs. 15.0 months, 95% CI 11.7−28.2; p = 0.02) and overall survival (30.6 months, 95% CI 12.4−37.2, vs. 55.6 months, 95% CI 25.8−61.8; p = 0.03) compared to those without detectable EGFR mutations. The detection of EGFR mutations in plasma ctDNA is a promising, minimally invasive, and reliable alternative to tumor biopsy, and the presence of EGFR mutations in plasma ctDNA after first-line EGFR-TKI therapy is associated with poor prognosis.

【 授权许可】

Unknown