Identification of metabolic signatures associated with erlotinib resistance of non-small cell lung cancer cells.
Identification of metabolic signatures associated with erlotinib resistance of non-small cell lung cancer cells.
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DOI：
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发表时间：
2014-06
影响因子：
2
通讯作者：
M. Serizawa;M. Kusuhara;Vincent Zangiacomi;K. Urakami;Masaru Watanabe;Toshiaki Takahashi;K. Yamaguchi;N. Yamamoto;Y. Koh
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文献类型：
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作者：
M. Serizawa;M. Kusuhara;Vincent Zangiacomi;K. Urakami;Masaru Watanabe;Toshiaki Takahashi;K. Yamaguchi;N. Yamamoto;Y. Koh
背景/目的获得对表皮生长因子受体(EGFR)酪氨酸激酶抑制剂(TKIs)的耐药性仍然是肺癌药物治疗的主要挑战。我们试图确定生物标记物，以早期检测对TKIs的耐药性。材料与方法采用毛细管电泳联用飞行时间质谱仪分析从EGFR突变型NSCLC细胞系PC-9建立的耐药的PC-9ER NSCLC细胞中与厄洛替尼耐药相关的代谢特征。结果PC-9ER细胞表现出谷氨酰胺代谢增强的代谢特征。V-myc禽髓细胞瘤病毒癌基因同源物(Myc)、谷胱甘肽-S转移酶(GSTT2)、γ-谷氨酰转移酶1(GGT1)和GGT5的拷贝数增加，提示这些基因的扩增与PC-9ER细胞对谷氨酰胺成瘾有关。结论谷氨酰胺代谢增强可作为预测EGFR-TKIs疗效的替代指标。
BACKGROUND/AIM The acquisition of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) remains a major challenge in lung cancer medicine. We sought to identify biomarkers for the early detection of resistance to TKIs. MATERIALS AND METHODS Capillary electrophoresis time-of-flight mass spectrometry analysis was performed to identify the metabolic signatures associated with erlotinib resistance in erlotinib-resistant PC-9ER NSCLC cells established from the EGFR-mutant NSCLC cell line PC-9. RESULTS PC-9ER cells showed metabolic signatures indicative of enhanced glutamine metabolism. Copy number gains in v-myc avian myelocytomatosis viral oncogene homolog (MYC), glutathione-S-transferase theta 2 (GSTT2), gamma-glutamyltransferase 1 (GGT1), and GGT5 were also detected, suggesting that amplification of these genes confers glutamine addiction in PC-9ER cells. CONCLUSION Enhanced glutamine metabolism may be a surrogate marker that can be used to predict the likelihood of patients to respond to EGFR-TKIs.