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极光激酶 A 多态性和表皮生长因子受体突变对肺腺癌临床病理特征的影响。

Impact of Aurora Kinase A Polymorphism and Epithelial Growth Factor Receptor Mutations on the Clinicopathological Characteristics of Lung Adenocarcinoma.

机构信息

School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.

Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung 402, Taiwan.

出版信息

Int J Environ Res Public Health. 2020 Oct 8;17(19):7350. doi: 10.3390/ijerph17197350.

Abstract

Lung adenocarcinoma (LADC) is the most common subtype of lung cancer worldwide and the epidermal growth factor receptor (EGFR) has a great influence on its clinical course, mainly due to the influence of different phenotypes. The Aurora kinase A (AURKA) would influence the progression of several solid malignancies. However, whether the interaction between EGFR phenotypes and AURKA would influence the clinical characteristics of LADC remains unknown. Herein, this study aimed to explore the effects of single-nucleotide polymorphisms (SNPs) of AURKA and EGFR phenotypes on the clinicopathological characteristics of LADC. Four loci of AURKA SNPs (, and ) were genotyped using TaqMan allelic discrimination in 105 wild-type EGFR individuals and 167 LADC patients with EGFR mutations. After the statistical analysis, patients with LADC who had CT heterozygotes of AURKA had a lower risk of EGFR mutations than patients with wild-type homozygotes. Moreover, female and nonsmoking patients who carried the CT genotype of AURKA had a lower risk of EGFR mutation ( = 0.008 and = 0.004, respectively). Moreover, in patients with EGFR mutations, AURKA SNP G allele (AG + GG) carriers had a lower risk of developing advanced-stage LADC (stage III or IV; odds ratio = 0.423, 95% confidence interval: 0.203-0.879, = 0.019) than patients with AA homozygotes. Our results suggested that AURKA variants are significantly associated with EGFR mutations among patients with LADC, particularly in female and nonsmoking patients. AURKA variants may contribute to the pathological development of LADC.

摘要

肺腺癌(LADC)是全球最常见的肺癌亚型,表皮生长因子受体(EGFR)对其临床过程有很大影响,主要是由于不同表型的影响。极光激酶 A(AURKA)会影响几种实体恶性肿瘤的进展。然而,EGFR 表型与 AURKA 之间的相互作用是否会影响 LADC 的临床特征尚不清楚。在此,本研究旨在探讨 AURKA 单核苷酸多态性(SNP)与 EGFR 表型之间的相互作用对 LADC 临床病理特征的影响。采用 TaqMan 等位基因鉴别法对 105 例野生型 EGFR 个体和 167 例 EGFR 突变的 LADC 患者的 AURKA 四个基因座(、和)进行 SNP 分型。经统计学分析,AURKA 杂合突变 CT 型患者的 LADC 发生 EGFR 突变的风险低于野生型纯合突变 CT 型患者。此外,携带 AURKA 杂合突变 CT 型的女性和非吸烟者患者发生 EGFR 突变的风险较低(=0.008 和=0.004)。此外,在携带 EGFR 突变的患者中,AURKA SNP G 等位基因(AG+GG)携带者发生晚期 LADC(III 期或 IV 期)的风险低于 AA 纯合子携带者(比值比=0.423,95%置信区间:0.203-0.879,=0.019)。我们的结果表明,AURKA 变异与 LADC 患者的 EGFR 突变显著相关,特别是在女性和非吸烟者中。AURKA 变异可能有助于 LADC 的病理发展。

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