1. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
2. Department of Pulmonary Medicine, Buddhist Tzu Chi General Hospital, Taipei Branch, New Taipei City, Taiwan
3. Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan
4. Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
5. Department of Chest Medicine, Cheng-Ching General Hospital, Taichung, Taiwan
6. School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan
7. Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, United States
8. Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
9. School of Medicine, Chung Shan Medical University, Taichung, Taiwan
10. Division of Chest, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
*These authors contributed equally to the work.
Epithelial-mesenchymal transition (EMT) was recently discovered related to the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in NSCLC patients and cell lines. In this study, we aimed to explore the association among the E-cadherin gene (CDH1) genetic variants, TK-domain mutations of EGFR, and clinicopathologic characteristics in patients with lung adenocarcinoma. A total of 280 patients with lung adenocarcinoma were recruited between years 2012 and 2015. All subjects underwent the analysis of CDH1 genetic variants (rs16260 and rs9929218) by real-time polymerase chain reaction (PCR) genotyping. The results showed that CA and CA + AA genotypes of CDH1 single nucleotide polymorphism (SNP) rs16260 were significantly reverse associated with EGFR mutation type (Adjusted odds ratio (AOR) = 0.43, 95% CI = 0.20-0.92 and AOR = 0.46, 95% CI = 0.22-0.96, respectively) in female lung adenocarcinoma patients. Moreover, the significantly reverse associations between CA and CA + AA genotypes of CDH1 rs16260 and EGFR hotspot mutations, namely L858R mutation and exon 19 in-frame deletion, were also demonstrated among female patients. Besides, CA + AA genotype of CDH1 rs16260 was noted significantly reverse associated with the tumor sizes (OR = 0.31, 95% CI = 0.12-0.80; p = 0.012). In conclusion, our results suggested that CDH1 variants are significantly reverse associated with mutation of EGFR tyrosine kinase, especially among the female patients with lung adenocarcinoma. The CDH1 variants might contribute to pathological development in lung adenocarcinoma.
Keywords: Adenocarcinoma, E-cadherin, CDH1 gene, Polymorphism, Genetic variants, Epidermal growth factor receptor