title: Phospholipids of tumor extracellular vesicles stratify gefitinib-resistant nonsmall cell lung cancer cells from gefitinib-sensitive cells.
abstract: 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 of the development of secondary activating mutations such as T790M in EGFR. Predicting chemo-responsiveness of cancer patients provides a major challenge in chemotherapy. The goal of the present study is to determine whether phospholipid signatures of tumor extracellular vesicles (EV) are associated with gefitinib-resistance of NSCLC. A sophisticated MS-based shotgun lipidomic assays were performed for in-depth analysis of the lipidomes of gefitinib-resistant (PC9R) and responsive (PC9) NSCLC cells and their shed EV from these cell lines (PC9EV or PC9REV). Lipid MALDI-MS analysis showed that EV phospholipid composition was significantly distinct in PC9R, compared to PC9 cells. Following statistical analyses has identified 35 (20 positive and 15 negative ion mode) differentially regulated lipids, which are significantly over- or underexpressed in PC9R EV, compared to PC9 EV (p value < 0.01, fold change > 1.5). Our phospholipid signatures suggest that EV associates with drug sensitivity, which is worthy of additional investigation to assess chemoresistance in patients with NSCLC treated with anti-EGFR TKIs.
authors.affiliation: Department of Applied Chemistry, College of Applied Science, Kyung Hee University, Yongin, Republic of Korea.
authors.forename: Jae Hun
authors.initials: JH
authors.lastname: Jung
authors.forename: Min Young
authors.initials: MY
authors.lastname: Lee
authors.forename: Do-Young
authors.initials: DY
authors.lastname: Choi
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Sungyong
authors.initials: S
authors.lastname: You
authors.forename: Kye Young
authors.initials: KY
authors.lastname: Lee
authors.forename: Jayoung
authors.initials: J
authors.lastname: Kim
authors.forename: Kwang Pyo
authors.initials: KP
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung; D002457:Cell Extracts / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D022162:Cytoplasmic Vesicles / Q000737:chemistry; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000502:physiology; D005110:Extracellular Space / Q000187:drug effects / Q000502:physiology; D000077156:Gefitinib; D006801:Humans; D010743:Phospholipids / Q000494:pharmacology / Q000502:physiology; D011799:Quinazolines / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D002457:Cell Extracts; D010743:Phospholipids; D011799:Quinazolines; D000077156:Gefitinib
keywords: Extracellular vesicles; Lipidopmics; MALDI-MS; Nonsmall-cell-lung cancer; Phospholipids