Clinical significance of human leukocyte antigen loss and melanoma-associated antigen 4 expression in smokers of non-small cell lung cancer patients

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• 作者：Tetsuro Baba (1)
  Hironobu Shiota (1)
  Koji Kuroda (1)
  Yoshiki Shigematsu (1)
  Yoshinobu Ichiki (1)
  Hidetaka Uramoto (1)
  Takeshi Hanagiri (1)
  Fumihiro Tanaka (1)
  
• 关键词：Non ; small cell lung cancer ; Smoking ; Tumor immunology ; Cancer/testis antigen ; HLA class I
• 刊名：International Journal of Clinical Oncology
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：18
• 期：6
• 页码：997-1004
• 全文大小：
• 作者单位：Tetsuro Baba (1)
  Hironobu Shiota (1)
  Koji Kuroda (1)
  Yoshiki Shigematsu (1)
  Yoshinobu Ichiki (1)
  Hidetaka Uramoto (1)
  Takeshi Hanagiri (1)
  Fumihiro Tanaka (1)
  
  1. Department of Surgery II, School of Medicine, University of Occupational and Environmental Health, Iseigaoka 1-1, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
  
• ISSN：1437-7772

文摘

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). Conclusion 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.