Epidermal growth factor receptor (EGFR)  mutations in non-small cell lung cancer (NSCLC) of Yunnan in southwestern  China

Zhou, Yunyun; Yang, Yunjun; Yang, Chen; Chen, Yunlan; Yang, Caiqin; Du, Yaxi; Guo, Yinjin; Ye, Lianhua; Huang, Yunchao

doi:10.18632/oncotarget.14706

Cited by 23 publications

(33 citation statements)

References 33 publications

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“…Next, in our clinical study, we observed a high clinical sensitivity (82.0%) and specificity (100%) of ADx-SuperARMS EGFR mutation blood testing. E19Dels and L858R were the two most common EGFR mutation subtypes in our study, just as reported in previous Chinese NSCLC studies[ 47 , 48 ]. Compared to the performance of ddPCR[ 30 ], ADx-SuperARMS provides a better sensitivity of E19Dels (88% vs. 82%) and L858R (89% vs. 80%) mutation detection in plasma with a specificity of 99% and 100% respectively.…”

Section: Discussionsupporting

confidence: 89%

Clinical validation of a highly sensitive assay to detect EGFR mutations in plasma cell-free DNA from patients with advanced lung adenocarcinoma

et al. 2017

PLoS ONE

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BackgroundCirculating tumor DNA (ctDNA) is a promising biomarker for noninvasive epidermal growth factor receptor (EGFR) mutations detection in lung cancer patients, but the existing methods have limitations in sensitivity or in availability. In this study, we evaluated the performance of a novel assay called ADx-SuperARMS in detecting EGFR mutations in plasma cell-free DNA from patients with advanced lung adenocarcinoma.MethodsA total of 109 patients with metastatic advanced adenocarcinoma were recruited who provided both blood samples and matched tumor tissue samples. EGFR mutation status in plasma samples were tested with ADx-SuperARMS EGFR assay and tumor tissue samples were tested with ADx-ARMS EGFR assay. The clinical sensitivity, specificity, positive prediction value (PPV), and negative prediction value (NPV) of ADx-SuperARMS EGFR assay were calculated by using EGFR mutation status in tumor tissue as standard reference. A receiver operating characteristic (ROC) analysis was implemented and an area under the curve (AUC) was calculated to evaluate sensitivity and specificity of exon 19 deletion (E19Del) and L858R mutation detection. The objective response rate (ORR) were calculated according to the EGFR mutation status determined by ADx-superARMS as well.Results0.2% analytical sensitivity and 100% specificity of the ADx-SuperARMS EGFR assays for EGFR E19Del, L858R, and T790M mutants were confirmed by using a series of diluted cell line DNA. In the clinical study, EGFR mutations were detected in 45.9% (50/109) of the plasma samples and in 56.9% (62/109) of the matched tumor tissue samples. The sensitivity, specificity, PPV and NPV of the ADx-SuperARMS EGFR assay for plasma EGFR mutation detection were 82.0% (50/61), 100% (48/48), 100% (50/50), and 81.4% (48/59), respectively. In ROC analysis, ADx-SuperARMS achieved sensitivity and specificity of 88% and 99% in E19Dels as well as sensitivity and specificity of 89% and 100% in L858R, respectively. Among the 35 patients who were plasma EGFR mutation positive and treated with first generation of EGFR-tyrosine kinase inhibitors (TKIs), 23 (65.7%) achieved partial response, 11 (31.4%) sustained disease, and 1 (2.9%) progressive disease. The ORR and disease control rate (DCR) were 65.7% and 97.1%, respectively.ConclusionsADx-SuperARMS EGFR assay is likely to be a highly sensitive and specific method to noninvasively detect plasma EGFR mutations of patients with advanced lung adenocarcinoma. The EGFR mutations detected by ADx-SuperARMS EGFR assay could predict the efficacy of the treatment with first generation of EGFR-TKIs. Hence, EGFR blood testing with ADx-SuperARMS could address the unmet clinical needs.

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Section: Discussionsupporting

confidence: 89%

Clinical validation of a highly sensitive assay to detect EGFR mutations in plasma cell-free DNA from patients with advanced lung adenocarcinoma

et al. 2017

PLoS ONE

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“…The patient cohort in the present study was primarily from Yunnan Province, an undeveloped, secluded and mountainous province of southwestern China, therefore a number of individuals in this region are unable to afford the relatively expensive cost of PET-CT and gene mutation detection, directly leading to the small sample size. Secondly, a bias could have existed in the process of the patient selection process since the majority of the patients resided in Yunnan Province that is known for high lung cancer rates (46)(47)(48). Thirdly, differences in metabolic parameters among different EGFR mutations, and between EGFR mutation and other important mutations (e.g.…”

Section: Discussionmentioning

confidence: 99%

EGFR mutation decreases FDG uptake in non‑small cell lung cancer via the NOX4/ROS/GLUT1 axis

et al. 2018

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[ 18 F]fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)-computed tomography (CT) is a functional imaging modality based on glucose metabolism. The association between the maximum standardized uptake value (SUV max) from 18 F-FDG PET-CT scanning and epidermal growth factor receptor (EGFR) mutation status has, to the best of our knowledge, not previously been fully elucidated, and the potential mechanisms by which EGFR mutations alter FDG uptake are largely unknown. A total of 157 patients who were pathologically diagnosed with non-small cell lung cancer (NSCLC) who underwent EGFR mutation testing and PET-CT pretreatment between June 2015 and October 2017 were retrospectively analyzed. χ 2 and univariate analyses were performed to identify the contributors to EGFR mutation. The receiver operating characteristic (ROC) curve was analyzed, and the area under the curve (AUC) was calculated. Glucose transporter 1 (GLUT1) and NADPH oxidase 4 (NOX4) expression, and reactive oxygen species (ROS) activity were detected in the A549 (wild-type), PC-9 (EGFR mutation-positive, EGFR exon 19del) and NCI-H1975 (EGFR mutation-positive, combined with L858R and T790M substitution) cell lines. A total of 109 patients who met the criteria were enrolled, and 63 of those tested as EGFR mutation-positive. The SUV max values were significantly lower in patients with EGFR mutations (mean, 6.52±0.38) compared with in patients with wild-type EGFR (mean, 9.37±0.31; P<0.001). Using univariate analysis, EGFR mutation status was significantly associated with sex, smoking status, tumor histology and SUV max of the primary tumor. In the multivariate analysis, smoking status (never-smoking), histopathology (adenocarcinoma) and SUV max (≤9.91) were the statistically significant predictors of EGFR mutations. ROC curve analysis identified that the SUV max cutoff point was 9.92, for which the AUC was 0.75 (95% confidence interval, 0.68-0.83). Reverse transcription-polymerase chain reaction indicated that the GLUT1 mRNA decreased in the PC-9 and NCI-H1975 cell lines compared with the A549 cell line (0.82±0.07 and 0.72±0.04 vs. 0.98±0.04, respectively; P<0.05) and decreased ROS activity was observed in the PC-9 cell line. Furthermore, the expression of NOX4 mRNA decreased by 20% in PC-9 (P<0.01) and by 14% (P<0.05) in NCI-H1975 cells. In addition, NOX4 protein expression decreased by 13% in PC-9 and by 16% in NCI-H1975 cells (both P<0.05) compared with the A549 cell line. The SUV max could be considered to effectively predict EGFR mutation status of patients with NSCLC, and the EGFR mutation status may alter FDG uptake partially via the NOX4/ROS/GLUT1 axis.

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“…Xuanwei City, in the northeastern part of Yunnan province, China, is 6,257 km 2 and lies on high plateau punctuated by mountain ridges 3 . Its total population is approximately one million.…”

Section: Introductionmentioning

confidence: 99%

Epidermal growth factor receptor T790M mutations in non-small cell lung cancer (NSCLC) of Yunnan in southwestern China

Zhou

Shi

et al. 2018

Sci Rep

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To explore the effect of epidermal growth factor receptor (EGFR) T790M mutation status on non-small cell lung cancer (NSCLC) in Yunnan province of southwestern China. First, this study used the super amplification refractory mutation system (Super ARMS) polymerase chain reaction (PCR) and Droplet Digital PCR (dd PCR) to evaluate the T790M gene mutation, in plasmatic ctDNA samples from 212 cases of NSCLC. The association between T790M mutations and clinical parameters were further explored. Next, to investigate the mechanism of drug resistance that resulted from T790M mutation, subgroup analyses according to duration of medicine (EGFR-TKIs) were carried out. Finally, we also evaluate the effectiveness of blood-based circulating tumor DNA (ctDNA) on detecting the T790M mutation by calculating Super ARMS’s detection efficiency. We found that the T790M mutation rate was 8.4% (18/212) in overall patients. The T790M mutation was more frequent in patients with brain metastasis 30.0% (12/40) (p < 0.01). We found that post-TKI samples 42.8% (15/35) were associated with a higher T790M mutation rate (p < 0.01). Subgroup analysis showed that the duration of TKI therapy for 6 to 10 months 66.6% (8/12) (p < 0.01) and >10 months 75.0% (9/12) (p < 0.01) were also associated with a higher T790M mutation rate. Super ARMS’s sensitivity, specificity, PPV, NPV, and accuracy were 100.0%, 99.4%, 94.7%, 100.0%, and 99.5% respectively. Generally, the EGFR-T790M mutation was more common in NSCLC patients with brain metastasis and those who received TKI therapy for more than 6 months. Moreover, Super ARMS is a sensitive, efficient, and practical clinic method for dynamically monitoring T790M mutation status and effectively guiding clinic treatment.

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Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) of Yunnan in southwestern China

Cited by 23 publications

References 33 publications

Clinical validation of a highly sensitive assay to detect EGFR mutations in plasma cell-free DNA from patients with advanced lung adenocarcinoma

Clinical validation of a highly sensitive assay to detect EGFR mutations in plasma cell-free DNA from patients with advanced lung adenocarcinoma

EGFR mutation decreases FDG uptake in non‑small cell lung cancer via the NOX4/ROS/GLUT1 axis

Epidermal growth factor receptor T790M mutations in non-small cell lung cancer (NSCLC) of Yunnan in southwestern China

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