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

Po-Jen Yang,Thomas Chang-Yao Tsao,Shun-Fa Yang,Hsiang-Ling Wang,Chi-Hua Yen,Ming-Ju Hsieh,Chia-Yi Lee,Chun-I Lee,Tu-Chen Liu,Whei-Ling Chiang

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 (rs1047972, rs2273535, rs6024836, and rs2064863) 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 rs1047972 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 rs1047972 had a lower risk of EGFR mutation (p = 0.008 and p = 0.004, respectively). Moreover, in patients with EGFR mutations, AURKA SNP rs6024836 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, p = 0.019) than patients with AA homozygotes. Our results suggested that AURKA rs1047972 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.

Highlights

Lung adenocarcinoma (LADC) is the most common subtype of lung cancer in both male and female patients [1]
Our results revealed that patients with LADC who had CT heterozygotes of Aurora kinase A (AURKA) rs1047972 had a lower risk of epidermal growth factor receptor (EGFR) mutations than patients with wild-type homozygotes
Regarding other clinicopathological characteristics of LADC, the distribution frequency of AURKA single-nucleotide polymorphisms (SNPs) rs6024836 was numerically higher in the mutated EGFR group with a lower tumor T status, absence of lymph node involvement, and negative distant metastasis. These results suggested that AURKA SNP rs6024836 creates its own universal effect in early cancer stages if it coexists with mutated EGFR phenotypes, and a study with more cases is warranted

Summary

Introduction

Lung adenocarcinoma (LADC) is the most common subtype of lung cancer in both male and female patients [1]. The global incidence rate (per 100,000 individuals) of LADC is 1.4 to 20.7 in males and 0.4 to 12.6 in females [2], and the female predominance of LADC over other lung cancers is noted globally and is the reason for LADC cases outnumbering those of lung squamous cell carcinoma [3]. Methyl-β-cyclodextrin can enhance the effect of doxorubicin on treating breast and liver cancers via influencing the p53 and Fas receptor ligand complex [5], and c-Fos expression may relate to the development of head and neck squamous cell carcinoma [6]. Target therapies that focus on specific phenotypes of LADC have been developed, and they target the mutation sites of tumor cells that include receptor tyrosine kinases, angiogenesis pathways, and the apoptosis process [4]

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