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J.W. Lee



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    P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      P2.04-014 - High Resolution Metabolomics to Discover the Potential Biomarkers in EGFR Mutated Lung Cancer (ID 2503)

      09:30 - 09:30  |  Author(s): J.W. Lee

      • Abstract
      • Slides

      Background:
      Lung cancer is the most common cause of cancer death in the world. The epidermal growth factor receptor (EGFR) is a key target in the treatment of advanced non-small cell lung cancer (NSCLC). EGFR tyrosine kinase inhibitors (EGFR TKIs) have shown good clinical efficacies in EGFR mutation positive patients. For the determination of lung cancer, biopsy has been the method of choice. However, this method is invasive and not safe. Therefore, non-invasive test for the detection of EGFR mutation is required for the safety of the patients. This study aims to discover novel biomarkers which could be utilized in clinical use in the non-invasive diagnosis of EGFR mutation among NSCLC patients.

      Methods:
      Plasma samples from 15 patients were analyzed to detect biomarkers of EGFR-activating mutations. All patients had histological confirmation of advanced NSCLC. EGFR mutations in tumor tissue were detected using the peptide nucleic acid (PNA)-mediated polymerase chain reaction (PCR) clamping method. Ten (66.7%) of the patients had EGFR mutations in tumor tissue. The mutation groups were divided into exon 21 deletion group (G2) (n=6), and exon 19 deletion group (G3) (n=4). Differences in metabolic profiles of EGFR mutation lung cancer populations and no mutation lung cancer patients (G1) (n=5) were examined through the use of high-throughput mass spectrometry.

      Results:
      A total of 216 significant metabolites were found to be different between non-mutated and mutated samples. It was found that patients with EGFR mutated NSCLC have a significantly lower levels of leucine. Comparison between G1 and G2 showed that L-proline levels of G2 patients were decreased. Lastly, the comparison between G1 and G3 showed that Butyryl-L-carnitine concentrations of G3 were decreased as compared to G1 patients.

      Conclusion:
      These findings may not only open a door to a thorough non-invasive diagnosis of an EGFR mutation but also a possibility to classify the type of mutation present. Our results show that changes in metabolite pattern are useful for in diagnosing EGFR mutation. One of the potential biomarkers, leucine discriminates EGFR-mutated lung cancer from that of non-mutated ones. Therefore, high resolution metabolomics can be the potential non-invasive tool to utilize clinically to detect the EGFR mutations in NSCLC patients.

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