title: Nuclear Y-box binding protein-1, a predictive marker of prognosis, is correlated with expression of HER2/ErbB2 and HER3/ErbB3 in non-small cell lung cancer.
abstract: BACKGROUND
  Nuclear expression of Y-box binding protein-1 (YB-1) is closely associated not only with global drug resistance and expression of several growth factor receptors in various human malignancies but also with overall patient survival.
  
  
  METHODS
  The effect of YB-1 knockdown on expression of epidermal growth factor receptor (EGFR) family proteins was examined by Western blot using human lung cancer cell lines. Immunohistochemistry was used to evaluate the expression of nuclear YB-1 and EGFR family proteins in patients with non-small cell lung cancer (NSCLC) (n = 104).
  
  
  RESULTS
  In the five NSCLC cell lines, expressions of EGFR, human epidermal growth factor receptor 2 (HER2), HER3, and hepatocyte growth factor receptor (c-Met) in PC-9 cells; of HER2 and c-Met in EBC-1 cells; and of HER3 in QG56 cells were down-regulated by YB-1 knockdown. By immunohistochemical analysis, we observed that HER3 expression was significantly negatively correlated with nuclear YB-1 expression in squamous cell carcinoma (p = 0.038). HER2 expression was positively correlated with nuclear YB-1 expression in adenocarcinoma (p = 0.052). Nuclear expression of YB-1 correlated with overall survival of all patients (p = 0.028) and of patients with adenocarcinoma (p = 0.007). Furthermore, there was a significant difference in therapeutic efficacies of gefitinib between patients with nuclear YB-1 expression and those with non-nuclear YB-1 expression in patients with NSCLC (p = 0.004, n = 26) but not between those with high and those with low expression of EGFR, HER2, HER3, and c-Met.
  
  
  CONCLUSIONS
  Nuclear YB-1 expression might be essential for the malignant phenotype in lung cancer patients and might be an important biomarker for the development of therapeutic strategy against NSCLC.
authors: Department of Pharmaceutical Oncology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors: Masaki
authors: M
authors: Kashihara
authors: Koichi
authors: K
authors: Azuma
authors: Akihiko
authors: A
authors: Kawahara
authors: Yuji
authors: Y
authors: Basaki
authors: Satoshi
authors: S
authors: Hattori
authors: Takashi
authors: T
authors: Yanagawa
authors: Yasuhiro
authors: Y
authors: Terazaki
authors: Shinzo
authors: S
authors: Takamori
authors: Kazuo
authors: K
authors: Shirouzu
authors: Hisamichi
authors: H
authors: Aizawa
authors: Kenji
authors: K
authors: Nakano
authors: Masayoshi
authors: M
authors: Kage
authors: Michihiko
authors: M
authors: Kuwano
authors: Mayumi
authors: M
authors: Ono
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry* / Q000188:drug therapy / Q000401:mortality; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000502:physiology; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D000077156:Gefitinib; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis* / Q000502:physiology; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis; D011799:Quinazolines / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D020893:Receptor, ErbB-3 / Q000032:analysis*; D051840:Y-Box-Binding Protein 1
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D066246:ErbB Receptors; D000077156:Gefitinib; D009687:Nuclear Proteins; D019859:Proto-Oncogene Proteins c-met; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; C508053:ERBB2 protein, human