Application of ddPCR in detection of the status and abundance of EGFR T790M mutation in the plasma samples of non-small cell lung cancer patients

• Published in: Frontiers in oncology Vol. 12; p. 942123
• Main Authors: Zhang, Hui, Hu, Yi, Wang, Yan, Song, Xia, Hu, Ying, Ma, Li, Yang, Xinjie, Li, Kun, Qin, Na, Wang, Jinghui, Lv, Jialin, Li, Xi, Zhang, Xinyong, Zhang, Quan, Wu, Yuhua, Yao, Guangyin, Zhang, Shucai
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 26.01.2023
• Subjects: ddPCR; EGFR T790M; NGS; Oncology; plasma; third-generation EGFR-TKIs; ddPCR; NGS; plasma; EGFR T790M; third-generation EGFR-TKIs
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2022.942123

The third-generation epidermal growth factor receptor ( ) -tyrosine kinase inhibitor (TKIs), such as osimertinib, designed for targeting the acquired drug-resistant mutation of T790M, was approved as the first-line therapy for advanced -mutated non-small cell lung cancer (NSCLC). Thus, detection of the T790M mutation for NSCLC is crucial. However, tissue samples are often difficult to obtain, especially in patients at advanced stages. This study assessed the performances of droplet digital polymerase chain reaction (ddPCR) and next-generation sequencing (NGS) in detecting T790M status and abundance in the plasma ctDNA samples of patients with NSCLC. We also explored the association between T790M status and abundance and the response to third-generation EGFR-TKIs. A total of 201 plasma samples with matched tissues, 821 plasma samples, and 56 patients who received third-generation EGFR-TKIs with response evaluation were included in this study. ddPCR and NGS were used to detect the mutation status and abundance of T790M in the tissues and/or blood samples. The results showed that the sensitivity and the specificity of T790M mutation status detected by ddPCR in plasma samples were 81.82% and 91.85%, respectively, compared with the tissue samples, with a consistency coefficient of 0.740. Among the 821 plasma samples, the positive rates of T790M detected by ddPCR and NGS were 34.2% (281/821) and 22.5% (185/821), respectively. With NGS results as the reference, the sensitivity and the specificity of ddPCR were 100% and 84.91%, respectively, and the consistency coefficient of the two methods was 0.717. In addition, we found that a higher T790M abundance was linked to a higher treatment response rate to the third-generation EGFR-TKIs regardless of the classification of the median value of 0.43% ( = 0.016) or average value of 3.16% ( = 0.010). Taking these data together, this study reveals that ddPCR is an alternatively potent method for the detection of T790M in the plasma samples of NSCLC patients.