EGFR R497K polymorphism is a favorable prognostic factor for advanced lung cancer
EGFR R497K polymorphism is a favorable prognostic factor for advanced lung cancer
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DOI：
10.1007/s00432-008-0464-5
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发表时间：
2009-02-01
影响因子：
3.6
通讯作者：
Fujii, Yoshitaka
中科院分区：
文献类型：
--
作者：
Sasaki, Hidefumi;Okuda, Katsuhiro;Fujii, Yoshitaka
据报道，表皮生长因子受体（EGFR）基因的R497 K多态性在配体结合、酪氨酸激酶激活和生长刺激中具有减弱的功能。另一方面，EGFR激酶域基因突变在非小细胞肺癌（NSCLC）中的作用已被研究，以预测其对吉非替尼或厄洛替尼的敏感性。我们调查了225例手术治疗的NSCLC患者的EGFR突变和/或R497 K多态性状态。纳入腺癌病例192例。采用PCR-RFLP方法分析EGFR基因第13外显子多态性的存在与否，发现225例肺癌患者中有95例EGFR基因在激酶域发生突变。在86.2%的患者中，存在纯合或杂合的Lys 497等位基因。R497 KEGFR基因型与肺癌患者的性别、吸烟状况、病理类型等临床病理特征无相关性，EGFR突变状态与肺癌患者的R497 KEGFR基因型无相关性。在淋巴结阴性患者中，R497 KEGFR基因型与疾病结局无关。然而，在淋巴结阳性患者中，R497 K EGFR与更好的总生存率显著相关。这种关联可归因于新辅助或辅助化疗。在46例接受吉非替尼治疗的NSCLC患者中，EGFR野生型（GG）患者和AG+AA患者的预后无差异。R497 KEGFR基因多态性可能与晚期肺癌预后良好相关，并与化疗敏感性相关。
It has been reported that the R497K polymorphism of the epidermal growth factor receptor (EGFR) gene has attenuated functions in ligand binding, tyrosine kinase activation, and growth stimulation. On other hand, EGFR gene mutations at kinase domain in non-small cell lung cancer (NSCLC) have been examined for their ability to predict sensitivity to gefitinib or erlotinib.We investigated the EGFR mutations and/or R497K polymorphism statuses in 225 surgically treated NSCLC cases. 192 adenocarcinoma cases were included. The presence or absence of EGFR polymorphism of exon 13 was analyzed by PCR-RFLP method.EGFR mutations at kinase domain were found from 95 of 225 lung cancer patients. In 86.2% of patients, homo- or heterozygous Lys497 allele was present. No correlation existed between R497K EGFR genotype and clinico-pathological features, such as gender, smoking status, and pathological subtypes.EGFR mutation status was not correlated with R497KEGFR genotype of lung cancers. In node-negative patients, R497KEGFR genotype was not correlated with disease outcome. In node-positive patients, however, R497K EGFR was significantly associated with better overall survival. This association was attributable to neo-adjuvant or adjuvant chemotherapy. In 46 total gefitinib treated NSCLC patients, the prognosis was not different between the EGFR wild type (GG) patients and AG+AA patients. R497KEGFR polymorphism might be associated with favorable prognosis of advanced lung cancers and correlated with chemosensitivity.