title: Impact of epidermal growth factor receptor gene expression level on clinical outcomes in epidermal growth factor receptor mutant lung adenocarcinoma patients taking first-line epidermal growth factor receptor-tyrosine kinase inhibitors.
abstract: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are first-choice treatments for advanced non-small-cell lung cancer patients harboring EGFR mutations. Although EGFR mutations are strongly predictive of patients' outcomes and their response to treatment with EGFR-TKIs, early failure of first-line therapy with EGFR-TKIs in patients with EGFR mutations is not rare. Besides several clinical factors influencing EGFR-TKI efficacies studied earlier such as the Eastern Cooperative Oncology Group performance status or uncommon mutation, we would like to see whether semi-quantify EGFR mutation gene expression calculated by 2-ΔΔctwas a prognostic factor in EGFR-mutant non-small cell lung cancer patients receiving first-line EGFR-TKIs. This retrospective study reviews 926 lung cancer patients diagnosed from January 2011 to October 2013 at the Kaohsiung Chang Gung Memorial Hospital in Taiwan. Of 224 EGFR-mutant adenocarcinoma patients, 148 patients who had 2-ΔΔctdata were included. The best cutoff values of 2-ΔΔctfor in-frame deletions in exon 19 (19 deletion) and a position 858 substituted from leucine (L) to an arginine (R) in exon 21 (L858R) were determined using receiver operating characteristic curves. Patients were divided into high and low 2-ΔΔctexpression based on the above cutoff level. The best cutoff point of 2-ΔΔctvalue of 19 deletion and L858R was 31.1 and 104.7, respectively. In all, 92 (62.1%) patients showed high 2-ΔΔctexpression and 56 patients (37.9%) low 2-ΔΔctexpression. The mean age was 65.6 years. Progression-free survival of 19 deletion mutant patients with low versus high expression level was 17.07 versus 12.04 months (P = 0.004), respectively. Progression-free survival of L858 mutant patients was 13.75 and 7.96 months (P = 0.008), respectively. EGFR-mutant lung adenocarcinoma patients with lower EGFR gene expression had longer progression-free survival duration without interfering overall survival.
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial, Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Huang-Chih
authors.initials: HC
authors.lastname: Chang
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial, Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Yu-Mu
authors.initials: YM
authors.lastname: Chen
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial, Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Chia-Cheng
authors.initials: CC
authors.lastname: Tseng
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial, Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Kuo-Tung
authors.initials: KT
authors.lastname: Huang
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial, Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Chin-Chou
authors.initials: CC
authors.lastname: Wang
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial, Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Yung-Che
authors.initials: YC
authors.lastname: Chen
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial, Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Chien-Hao
authors.initials: CH
authors.lastname: Lai
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial, Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.|2 Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi, Taiwan.
authors.forename: Wen-Feng
authors.initials: WF
authors.lastname: Fang
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial, Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Hsu-Ching
authors.initials: HC
authors.lastname: Kao
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial, Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Meng-Chih
authors.initials: MC
authors.lastname: Lin
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000369:Aged, 80 and over; D049109:Cell Proliferation; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR mutation; Lung cancer adenocarcinoma; oncogene; polymerase chain reaction (PCR); tyrosine kinase inhibitors