The relationship between KRAS gene mutations and HLA class I antigen downregulation in the metastasis of non-small cell lung cancer
The relationship between KRAS gene mutations and HLA class I antigen downregulation in the metastasis of non-small cell lung cancer
复制标题
非小细胞肺癌转移中KRAS基因突变与HLA I类抗原下调的关系
DOI：
10.1177/0300060513489801
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发表时间：
2013-10-01
影响因子：
1.6
通讯作者：
Jiang, Wen-Peng
中科院分区：
文献类型：
--
作者：
He, Xiao-Peng;Song, Fu-Jie;Jiang, Wen-Peng
目的探讨非小细胞肺癌（NSCLC）患者原发肺肿瘤和转移淋巴结中v-Ki-ras 2 Kirsten大鼠肉瘤病毒癌基因同源物（KRAS）基因突变与人类白细胞抗原（HLA）I类抗原水平的关系。方法选择接受肿瘤切除术的NSCLC患者。使用聚合酶链反应-限制性片段长度多态性分析，分析了正常肺和淋巴结组织、原发性肺肿瘤和转移性淋巴结中的KRAS密码子12突变。采用流式细胞术检测HLA I类抗原免疫染色。结果共65例患者参加了研究。所有正常肺组织HLA-I类抗原免疫组化染色均为阳性。大多数原发性肺肿瘤（56/65）和所有转移性淋巴结（31/31）的HLA I类抗原免疫染色下调。原发肿瘤和转移淋巴结中HLA I类抗原表达下调之间呈正相关。原发性和转移性肿瘤中KRAS密码子12突变与HLA I类抗原水平呈负相关。结论KRAS基因第12密码子突变在NSCLC患者HLA I类抗原表达下调中起重要作用。致癌KRAS通路的异常激活可能为NSCLC提供新的治疗靶点。
Objective To investigate the association between v-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue (KRAS) gene mutations and levels of human leucocyte antigen (HLA) class I antigen in primary lung tumours and metastatic lymph nodes of patients with non-small cell lung cancer (NSCLC). Methods Patients with NSCLC undergoing tumour resection were enrolled. KRAS codon 12 mutations were analysed in normal lung and lymph node tissue, primary lung tumours and metastatic lymph nodes using polymerase chain reaction–restriction fragment length polymorphism analysis. HLA class I antigen immunostaining was examined using flow cytometry. Results A total of 65 patients participated in the study. All normal lung tissues had positive HLA class I antigen immunostaining. The majority of primary lung tumours (56/65) and all of the metastatic lymph nodes (31/31) had downregulated HLA class I antigen immunostaining. There was a positive correlation between downregulated HLA class I antigen in primary tumours and metastatic lymph nodes. There was a negative correlation between KRAS codon 12 mutations and the level of HLA class I antigen in primary and metastatic tumours. Conclusions KRAS codon 12 mutations appear to be important in the downregulation of HLA class I antigen in NSCLC. Abnormal activation of the oncogenic KRAS pathway might provide a new treatment target for NSCLC.