title: Anterior gradient 2 is correlated with EGFR mutation in lung adenocarcinoma tissues.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) has demonstrated a promising therapeutic response in lung adenocarcinoma patients with EGFR gene mutations. However, the predictive factors for this therapy have not been established, except for the EGFR gene mutation status of carcinoma cells.
  
  
  METHODS
  We first performed microarray analysis in EGFR-TKI-sensitive lung adenocarcinoma cell lines. The results indicated anterior gradient 2 (AGR2) as a potential surrogate marker of EGFR-TKI. Therefore, we then evaluated the correlation between the status of AGR2 immunoreactivity and clinicopathological factors including overall survival (OS), progression-free survival (PFS) and clinical response to EGFR-TKI, in 147 cases of surgically resected lung adenocarcinoma. The biological significance of AGR2 was further evaluated by transfecting small interfering RNA (siRNA) against AGR2 in these cells.
  
  
  RESULTS
  The status of AGR2 immunoreactivity was significantly higher in lung adenocarcinoma cases with EGFR gene mutations than in those with the wild type (p<0.0001), but there were no significant differences in OS, PFS and response of EGFR-TKI between the AGR2 high and low carcinoma cases. Knockdown of AGR2 gene expression following siRNA transfection resulted in a significantly lower response to EGFR-TKI in EGFR-mutated PC-3.
  
  
  CONCLUSIONS
  AGR2 could serve as an adjunctive surrogate protein marker possibly reflecting EGFR gene mutations in lung adenocarcinoma patients. Results from in vitro analysis indicated that AGR2 could be a potential clinical biomarker of EGFR-TKI therapeutic sensitivity in lung adenocarcinoma cells.
authors: 2 Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai - Japan.
authors: Sodai
authors: S
authors: Narumi
authors: Yasuhiro
authors: Y
authors: Miki
authors: Shuko
authors: S
authors: Hata
authors: Masahito
authors: M
authors: Ebina
authors: Mikiyoshi
authors: M
authors: Saito
authors: Kazushige
authors: K
authors: Mori
authors: Makoto
authors: M
authors: Kobayashi
authors: Takashi
authors: T
authors: Suzuki
authors: Erina
authors: E
authors: Iwabuchi
authors: Ikuro
authors: I
authors: Sato
authors: Makoto
authors: M
authors: Maemondo
authors: Chiaki
authors: C
authors: Endo
authors: Akira
authors: A
authors: Inoue
authors: Takashi
authors: T
authors: Kondo
authors: Hisafumi
authors: H
authors: Yamada-Okabe
authors: Masakazu
authors: M
authors: Ichinose
authors: Hironobu
authors: H
authors: Sasano
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D009154:Mutation; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D014162:Transfection
chemical_list: D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors