RT Journal Article
SR Electronic
T1 A polymorphism, which exists intronic lesion of <em>SLC5A10</em>, affects <em>DRG2</em> expression and survival outcome of early-stage non-small cell lung cancer
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP PA4242
DO 10.1183/13993003.congress-2015.PA4242
VO 46
IS suppl 59
A1 So Yeon Lee
A1 Seung Soo Yoo
A1 Mi Jung Hong
A1 Hye Won Seo
A1 Yong Dae Lee
A1 Keum Ju Choi
A1 Jin Eun Choi
A1 Hyo Gyoung Kang
A1 Yangki Seok
A1 Eung Bae Lee
A1 Kyung Min Shin
A1 Ji Yun Jeong
A1 Won Kee Lee
A1 Shin Yup Lee
A1 Jaehee Lee
A1 Seung Ick Cha
A1 Chang Ho Kim
A1 Young Tae Kim
A1 Sanghoon Jheon
A1 Jae Yong Park
YR 2015
UL http://erj.ersjournals.com/content/46/suppl_59/PA4242.abstract
AB RegulomeDB is a new tool that can predict regulatory functions of genetic variants. We investigated the association between putative functional variants selected using RegulomeDB and survival outcome of non-small cell lung cancer (NSCLC) via two independent cohort study. Total 244 variants with category 1a, which have the most confident evidence of variants affecting gene expression using RegulomeDB, were genotyped. Fourteen variants associated with overall survival (P &lt; 0.05) in discovery cohort were selected and examined using the validation cohort. One variant (rs2257609 C&gt;T) was validated. In a combined analysis, patients with rs2257609 CT or TT genotype exhibited a worse overall survival and disease free survival than those with rs2257609 CC genotype (hazard ratio [HR] = 1.87, 95% confidence interval [CI] = 1.41 – 2.48, P = 2.0 × 10-5 and HR = 1.44, 95% CI = 1.16 – 1.79, P = 0.001, respectively). DRG2 expression, which was predicted to be affected by rs2257609, was significantly higher in tumor tissues than non-malignant lung tissues (P = 0.001) and was different according to the rs2257609 genotype (Ptrend = 0.03). ). Luciferase assay also revealed higher promoter activity of DRG2 with rs2257609 T allele (P = 0.03). These results suggest that the rs2257609 C&gt;T may affect DRG2 expression and can be used as prognostic marker in early-stage NSCLC patients.