|Quantification and Dynamic Monitoring of EGFR T790M in Plasma Cell-Free DNA by Digital PCR for Prognosis of EGFR-TKI Treatment in Advanced NSCLC|
|Wang, Zhijie; Chen, Rui; Wang, Shuhang; Zhong, Jia; Wu, Meina; Zhao, Jun; Duan, Jianchun; Zhuo, Minglei; An, Tongtong; Wang, Yuyan; Bai, Hua1; Wang, Jie|
|WOS标题词||Science & Technology|
|研究领域[WOS]||Science & Technology - Other Topics|
|关键词[WOS]||TYROSINE KINASE INHIBITOR ; FACTOR RECEPTOR MUTATIONS ; LUNG-CANCER PATIENTS ; ACQUIRED-RESISTANCE ; NONINVASIVE DETECTION ; 1ST-LINE TREATMENT ; OPEN-LABEL ; GEFITINIB ; ERLOTINIB ; CHEMOTHERAPY|
Background: Among advanced non-small cell lung cancer (NSCLC) patients with an acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI), about 50% carry the T790M mutation, but this frequency in EGFR-TKI-naive patients and dynamic change during therapy remains unclear. This study investigated the quantification and dynamic change of T790M mutation in plasma cell-free DNA (cf-DNA) of advanced NSCLC patients to assess the clinical outcomes of EGFR-TKI therapy.
Materials and Methods: We retrospectively investigated 135 patients with advanced NSCLC who obtained progression-free survival (PFS) after EGFR-TKI for.6 months for their EGFR sensitive mutations and T790M mutation in matched pre-and post-TKI plasma samples, using denaturing high-performance liquid chromatography (DHPLC), amplification refractory mutation system (ARMS), and digital-PCR (D-PCR). Real-time PCR was performed to measure c-MET amplification.
Results: Detection limit of D-PCR in assessing the T790M mutation was approximately 0.03%. D-PCR identified higher frequency of T790M than ARMS in pre-TKI (31.3% vs. 5.5%) and post-TKI (43.0% vs. 25.2%) plasma samples. Patients with pre-TKI T790M showed inferior PFS (8.9 vs. 12.1 months, p = 0.007) and overall survival (OS, 19.3 vs. 31.9 months, p = 0.001) compared with those without T790M. In patients harboring EGFR sensitive mutation, high quantities of pre-TKI T790M predicted poorer PFS (p = 0.001) on EGFR-TKI than low ones. Moreover, patients who experienced increased quantity of T790M during EGFR-TKI treatment showed superior PFS and OS compared with those with decreased changes (p = 0.044 and p = 0.015, respectively).
Conclusion: Qualitative and quantitative T790M in plasma cf-DNA by D-PCR provided a non-invasive and sensitive assay to predict EGFR-TKI prognosis.
|项目编号||81025012 ; 81330062 ; IRT13003 ; 320.6750.1361 ; 320.6750.12192|
|资助机构||National Natural Science Foundation Distinguished Young Scholars ; National Natural Science Foundation Key Program ; Education Ministry Innovative Research Team Program ; Peking University-Tsinghua University Joint Center ; Wujieping Medicine Foundation|
|作者单位||1.Beijing Inst Canc Res, Beijing, Peoples R China|
2.Beijing Canc Hosp, Minist Educ, Key Lab Carcinogenesis & Translat Res, Dept Thorac Med Oncol, Beijing, Peoples R China
|Wang, Zhijie,Chen, Rui,Wang, Shuhang,et al. Quantification and Dynamic Monitoring of EGFR T790M in Plasma Cell-Free DNA by Digital PCR for Prognosis of EGFR-TKI Treatment in Advanced NSCLC[J]. PLOS ONE,2014,9(11).|
|APA||Wang, Zhijie.,Chen, Rui.,Wang, Shuhang.,Zhong, Jia.,Wu, Meina.,...&Wang, Jie.(2014).Quantification and Dynamic Monitoring of EGFR T790M in Plasma Cell-Free DNA by Digital PCR for Prognosis of EGFR-TKI Treatment in Advanced NSCLC.PLOS ONE,9(11).|
|MLA||Wang, Zhijie,et al."Quantification and Dynamic Monitoring of EGFR T790M in Plasma Cell-Free DNA by Digital PCR for Prognosis of EGFR-TKI Treatment in Advanced NSCLC".PLOS ONE 9.11(2014).|