Clinical significance of human leukocyte antigen loss and melanoma-associated antigen 4 expression in smokers of non-small cell lung cancer patients
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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DOI：
10.1007/s10147-012-0491-8
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发表时间：
2013-12-01
影响因子：
3.3
通讯作者：
Tanaka, Fumihiro
中科院分区：
文献类型：
--
作者：
Baba, Tetsuro;Shiota, Hironobu;Tanaka, Fumihiro
黑色素瘤相关抗原-A4（MAGE-A4）是免疫治疗的候选靶点之一，在非小细胞肺癌（NSCLC）中表达。然而，肿瘤有时会丧失人类白细胞抗原（HLA）I类表达，并且肿瘤特异性T细胞不能消除HLA丧失的肿瘤。本文对363例连续行根治性手术的NSCLC患者中187例资料可供分析的病例进行回顾性分析。免疫组化染色检测HLA I类分子的表达。RT-PCR检测MAGE-A4的表达，77例肿瘤HLA表达正常，110例肿瘤HLA表达缺失。HLA缺失患者中有吸烟习惯和表达MAGE-A4基因的患者比例高于HLA表达患者（分别为p = 0.04和0.028）。表达MAGE-A4但HLA缺失的患者的5年总生存率（OS）为52.4%，OS显著低于其对应者（74.0%，p = 0.036）。多因素分析显示，晚期或有吸烟史、HLA I类基因缺失是NSCLC患者OS预后不良的独立预测因子（分别为p < 0.01和p = 0.04），HLA I类基因缺失与吸烟史、肿瘤组织MAGE-A4表达有关。吸烟者或携带MAGE-A4基因患者的HLA I类缺失是NSCLC的预后因素。
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.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.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).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.