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 Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
6. School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan
7. Department of Chest Medicine, Cheng-Ching General Hospital, Taichung, Taiwan
8. School of Medicine, Chung Shan Medical University, Taichung, Taiwan
9. Division of Chest, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
#These authors contributed equally to the work.
EGFR mutation of Non-small cell lung cancers (NSCLC) was predominantly seen in Asian population and it was considered as a predictor of responsiveness. Eendothelial nitric oxide synthase (eNOS) plays a vital role in chronic inflammation and carcinogenesis. In this study, we aimed to explore the association between the genetic polymorphisms of eNOS (-786T/C and 894 G/T) and EGFR mutation in patients with lung adenocarcinoma. A total of 277 patients with diagnosed lung adenocarcinoma were recruited between years 2012 and 2015. All study subjects underwent the analysis of eNOS genetic variants (-786 T/C and 894 G/T) using real-time polymerase chain reaction (PCR) genotyping. Our results showed that, among the 277 patients, variant types (GT + TT) of eNOS 894 G/T polymorphism were significantly positively correlated with EGFR mutation type, specifically exon 19 in-frame deletion. With the subgroup of EGFR L858R mutation, variant genotypes (GT + TT) of eNOS 894 G/T were significantly associated with lymph node invasion. Moreover, in silico analysis indicated that eNOS 894 G/T altered the eNOS expression. In conclusion, our study showed that eNOS 894 G/T variants were significantly associated with EGFR mutation types of lung adenocarcinoma, specifically exon 19 in-frame deletion. This may be utilized as a prediction of tumor invasiveness and therapy responsiveness.
Keywords: Adenocarcinoma, Lung cancer, Endothelial nitric oxide synthase (eNOS) gene, Polymorphism, Epidermal growth factor receptor (EGFR)