Detection of EGFR Somatic Mutations in Non-Small Cell Lung Cancer (NSCLC) Using a Novel Mutant-Enriched Liquidchip (MEL) Technology

Zhang, Li; Yang, Huiyi; Zhao, Yanbin; Li, Wenchao; Wu, Shiyang; He, Jinzhi; Luo, Xiaodi; Zhu, Zhengyan; Xu, Jianbing; Zhou, Qinghua; Ren-Heidenreich, Lifen

doi:10.2174/138920012802138660

Cited by 11 publications

(9 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, it is 59 in our study, which is much lower than 71. Although the median age in Asia has been reported as lower than 71 before (Xu et al , 2011; Zhang et al , 2012), more young patients with NSCLC in China than the western countries may be the reason for the low median age. According to an internet database from 1381 hospitals, there is only 0.7% lung cancer at the age group <40 years (Age Group of Lung Cancer Diagnosed, 2000–2007).…”

Section: Discussionmentioning

confidence: 83%

Coexistence of EGFR with KRAS, or BRAF, or PIK3CA somatic mutations in lung cancer: a comprehensive mutation profiling from 5125 Chinese cohorts

et al. 2014

View full text Add to dashboard Cite

Background:Determining the somatic mutations of epidermal growth factor receptor (EGFR)-pathway networks is the key to effective treatment for non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitors (TKIs).The somatic mutation frequencies and their association with gender, smoking history and histology was analysed and reported in this study.Methods:Five thousand one hundred and twenty-five NSCLC patients' pathology samples were collected, and EGFR, KRAS, BRAF and PIK3CA mutations were detected by multiplex testing. The mutation status of EGFR, KRAS, BRAF and PIK3CA and their association with gender, age, smoking history and histological type were evaluated by appropriate statistical analysis.Results:EGFR, KRAS, BRAF and PIK3CA mutation rates revealed 36.2%, 8.4%, 0.5% and 3.3%, respectively, across the 5125 pathology samples. For the first time, evidence of KRAS mutations were detected in two female, non-smoking patients, age 5 and 14, with NSCLC. Furthermore, we identified 153 double and coexisting mutations and 7 triple mutations. Interestingly, the second drug-resistant mutations, T790M or E545K, were found in 44 samples from patients who had never received TKI treatments.Conclusions:EGFR exons 19, 20 and 21, and BRAF mutations tend to happen in females and non-smokers, whereas KRAS mutations were more inclined to males and smokers. Activating and resistant mutations to EGFR-TKI drugs can coexist and ‘second drug-resistant mutations', T790M or E545K, may be primary mutations in some patients. These results will help oncologists to decide candidates for mutation testing and EGFR-TKI treatment.

show abstract

Section: Discussionmentioning

confidence: 83%

Coexistence of EGFR with KRAS, or BRAF, or PIK3CA somatic mutations in lung cancer: a comprehensive mutation profiling from 5125 Chinese cohorts

et al. 2014

View full text Add to dashboard Cite

show abstract

“…As shown in Figure 1, after primary screening, 34 full-text articles10131415162223242526272829303132333435363738394041424344454647484950 were selected for further evaluation of eligibility. By rigorous evaluation, 20 eligible studies were identified and included in meta-analysis1314151622232425262728293031323334353637.…”

Section: Resultsmentioning

confidence: 99%

Diagnostic value of circulating free DNA for the detection of EGFR mutation status in NSCLC: a systematic review and meta-analysis

Luo

Shen

Zheng

2014

Sci Rep

191

128

View full text Add to dashboard Cite

Epidermal growth factor receptor (EGFR) mutation is a reliable and sensitive biomarker for EGFR-TKI therapy in non-small-cell lung cancer (NSCLC). However, detection of EGFR mutation in tissues has obvious limitations. Circulating free DNA (cfDNA) has been reported as an alternative approach for the detection of EGFR mutations. This systematic review and meta-analysis was designed to assess the diagnostic performance of cfDNA, compared with tissues. True-positive (TP), false-positive (FP), false-negative (FN), and true-negative (TN) values were extracted or calculated for each study. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated. A summary receiver operating characteristic curve (SROC) and area under curve (AUC) were used to evaluate the overall diagnostic performance. 20 eligible studies involving 2012 cases were included in this meta-analysis. The pooled sensitivity, specificity, PLR, NLR, andDORwere 0.674 (95%CI: 0.517–0.800), 0.935 (95%CI: 0.888–0.963), 10.307 (95%CI: 6.167–17.227), 0.348 (95%CI: 0.226–0.537), and 29.582 (95%CI: 4.582–60.012), respectively. The AUC was 0.93 (95% CI: 0.90–0.95). The meta-analysis suggests that detection of EGFR mutation by cfDNA is of adequate diagnostic accuracy and cfDNA analysis could be a promising screening test for NSCLC.

show abstract

“…For patients who provided pretreatment samples, the presence of EGFR mutations in blood may correlate with severe tumor burden, which contributes to higher proportion of tumor-derived cfDNA. Zhao et al and Zhang et al found that there were more detectable EGFR mutations in plasma from patients with advanced disease or patients with poorly differentiated tumors [21], [35]. Park et al reported that tumor burden was predictive of inferior survival in NSCLC patients with EGFR mutant tumor who received gefitinib [36].…”

Section: Discussionmentioning

confidence: 99%

Peripheral Blood for Epidermal Growth Factor Receptor Mutation Detection in Non-Small Cell Lung Cancer Patients

Ren

et al. 2014

Translational Oncology

View full text Add to dashboard Cite

OBJECTIVE: It is important to analyze and track Epidermal Growth Factor Receptor (EGFR) mutation status for predicting efficacy and monitoring resistance throughout EGFR-tyrosine kinase inhibitors (TKIs) treatment in non-small cell lung cancer (NSCLC) patients. The objective of this study was to determine the feasibility and predictive utility of EGFR mutation detection in peripheral blood. METHODS: Plasma, serum and tumor tissue samples from 164 NSCLC patients were assessed for EGFR mutations using Amplification Refractory Mutation System (ARMS). RESULTS: Compared with matched tumor tissue, the concordance rate of EGFR mutation status in plasma and serum was 73.6% and 66.3%, respectively. ARMS for EGFR mutation detection in blood showed low sensitivity (plasma, 48.2%; serum, 39.6%) but high specificity (plasma, 95.4%; serum, 95.5%). Treated with EGFR-TKIs, patients with EGFR mutations in blood had significantly higher objective response rate (ORR) and insignificantly longer progression-free survival (PFS) than those without mutations (ORR: plasma, 68.4% versus 38.9%, P = 0.037; serum, 75.0% versus 39.5%, P = 0.017; PFS: plasma, 7.9 months versus 6.1 months, P = 0.953; serum, 7.9 months versus 5.7 months, P = 0.889). In patients with mutant tumors, those without EGFR mutations in blood tended to have prolonged PFS than patients with mutations (19.7 months versus 11.0 months, P = 0.102). CONCLUSIONS: EGFR mutations detected in blood may be highly predictive of identical mutations in corresponding tumor, as well as showing correlations with tumor response and survival benefit from EGFR-TKIs. Therefore, blood for EGFR mutation detection may allow NSCLC patients with unavailable or insufficient tumor tissue the opportunity to benefit from personalized treatment. However, due to the high false negative rate in blood samples, analysis for EGFR mutations in tumor tissue remains the gold standard.

show abstract

Detection of EGFR Somatic Mutations in Non-Small Cell Lung Cancer (NSCLC) Using a Novel Mutant-Enriched Liquidchip (MEL) Technology

Cited by 11 publications

References 0 publications

Coexistence of EGFR with KRAS, or BRAF, or PIK3CA somatic mutations in lung cancer: a comprehensive mutation profiling from 5125 Chinese cohorts

Coexistence of EGFR with KRAS, or BRAF, or PIK3CA somatic mutations in lung cancer: a comprehensive mutation profiling from 5125 Chinese cohorts

Diagnostic value of circulating free DNA for the detection of EGFR mutation status in NSCLC: a systematic review and meta-analysis

Peripheral Blood for Epidermal Growth Factor Receptor Mutation Detection in Non-Small Cell Lung Cancer Patients

Contact Info

Product

Resources

About