Phospholipids of tumor extracellular vesicles stratify gefitinib-resistant nonsmall cell lung cancer cells from gefitinib-sensitive cells.

摘要: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) such as gefitinib are one of gold standard treatment options for nonsmall-cell lung cancer (NSCLC) patients, which eventually fail due to the acquired resistance and relapse because development secondary activating mutations T790M in EGFR. Predicting chemo-responsiveness patients provides a major challenge chemotherapy. The goal present study is determine whether phospholipid signatures tumor extracellular vesicles (EV) associated with gefitinib-resistance NSCLC. A sophisticated MS-based shotgun lipidomic assays were performed in-depth analysis lipidomes gefitinib-resistant (PC9R) responsive (PC9) NSCLC cells their shed EV from these cell lines (PC9EV or PC9REV). Lipid MALDI-MS showed that composition was significantly distinct PC9R, compared PC9 cells. Following statistical analyses has identified 35 (20 positive 15 negative ion mode) differentially regulated lipids, over- underexpressed PC9R EV, (p value 1.5). Our suggest associates drug sensitivity, worthy additional investigation assess chemoresistance treated anti-EGFR TKIs.