title: Clinical significance of human leukocyte antigen loss and melanoma-associated antigen 4 expression in smokers of non-small cell lung cancer patients.
abstract: BACKGROUND
  Melanoma-associated antigen-A4 (MAGE-A4) is one of the candidates for a target of immunotherapy and is expressed in non-small cell lung cancer (NSCLC). However, tumors sometimes lose human leukocyte antigen (HLA) class I expression, and tumor-specific T cells cannot eliminate the tumor with loss of HLA. However, the relationship between MAGE-A4 expression and HLA loss has remained unclear.
  
  
  METHODS
  Among 363 NSCLC patients who consecutively underwent curative surgery, 187 cases whose material could be analyzed were reviewed. The expression of HLA class I molecules was assessed by immunohistochemical staining. The expression of MAGE-A4 was analyzed by RT-PCR.
  
  
  RESULTS
  Seventy-seven tumors expressed HLA normally; however, 110 tumors lost HLA. The proportion of patients with a smoking habit and expressing the MAGE-A4 gene in patients with HLA loss was higher than those with HLA expression (p = 0.04 and 0.028, respectively). Five-year overall survival (OS) rate in the patients expressing MAGE-A4 but with loss of HLA was 52.4 %, and OS was significantly poorer than their counterparts (74.0 %, p = 0.036). Multivariate analysis indicated that advanced stage or history of smoking and HLA loss was an independently poor prognostic predictor of OS in NSCLC (p < 0.01 and p = 0.04, respectively).
  
  
  CONCLUSIONS
  HLA class I loss in NSCLC was related to smoking history and MAGE-A4 expression of tumors. HLA class I loss in smokers or patients with the MAGE-A4 gene was a prognostic factors in NSCLC.
authors.affiliation: Department of Surgery II, School of Medicine, University of Occupational and Environmental Health, Iseigaoka 1-1, Yahatanishi-ku, Kitakyushu, 807-8555, Japan, t-baba@med.uoeh-u.ac.jp.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Baba
authors.forename: Hironobu
authors.initials: H
authors.lastname: Shiota
authors.forename: Koji
authors.initials: K
authors.lastname: Kuroda
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Shigematsu
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Ichiki
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Uramoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hanagiri
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Tanaka
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D006680:HLA Antigens / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D009367:Neoplasm Staging; D011379:Prognosis; D012907:Smoking / Q000009:adverse effects; D016019:Survival Analysis
chemical_list: D000951:Antigens, Neoplasm; D006680:HLA Antigens; C095204:MAGEA4 protein, human; D009363:Neoplasm Proteins