A pilot study identifying a potential plasma biomarker for determining EGFR mutations in exons 19 or 21 in lung cancer patients

Pamungkas,Aryo  D.; Medriano,Carl  A.; Sim,Eunjung; Lee,Sungyong; Park,Youngja  H.

doi:10.3892/mmr.2017.6530

A pilot study identifying a potential plasma biomarker for determining EGFR mutations in exons 19 or 21 in lung cancer patients

Authors:
- Aryo D. Pamungkas
- Carl A. Medriano
- Eunjung Sim
- Sungyong Lee
- Youngja H. Park
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Affiliations: College of Pharmacy, Korea University, Jochiwon‑eup, Sejong 30029, Republic of Korea, Department of Pulmonology, Korea University Guro Hospital, Guro‑gu, Seoul 08308, Republic of Korea
Published online on: April 28, 2017 https://doi.org/10.3892/mmr.2017.6530
Pages: 4155-4161
Copyright: © Pamungkas et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The most common type of lung cancer is non‑small cell lung cancer (NSCLC), which is frequently characterized by a mutation in the epidermal growth factor receptor (EGFR). Determining the presence of an EGFR mutation in lung cancer is important, as it determines the type of treatment that a patients will receive. Therefore, the aim of the present study was to apply high‑resolution metabolomics (HRM) using liquid chromatography‑mass spectrometry to identify significant compounds in human plasma samples obtained from South Korean NSCLC patients, as potential biomarkers for providing early detection and diagnosis of minimally‑invasive NSCLC. The metabolic differences between lung cancer patients without EGFR mutations were compared with patients harboring EGFR mutations. Univariate analysis was performed, with a false discovery rate of q=0.05, in order to identify significant metabolites between the two groups. In addition, hierarchical clustering analysis was performed to discriminate between the metabolic profiles of the two groups. Furthermore, the significant metabolites were identified and mapped using Mummichog software, in order to generate a potential metabolic network model. Using metabolome‑wide association studies, metabolic alterations were identified. Linoleic acid [303.23 m/z, (M+Na)+], 5‑methyl tetrahydrofolate [231.10 m/z, (M+2H)+] and N‑succinyl‑L‑glutamate‑5 semialdehyde [254.06 m/z, (M+Na)+], were observed to be elevated in patients harboring EGFR mutations, whereas tetradecanoyl carnitine [394.29 m/z, (M+Na)+] was observed to be reduced. This suggests that these compounds may be affected by the EGFR mutation. In conclusion, the present study identified four potential biomarkers in patients with EGFR mutations, using HRM combined with pathway analysis. These results may facilitate the development of novel diagnostic tools for EGFR mutation detection in patients with lung cancer.

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