Functional intronic variant of SLC5A10 affects DRG2 expression and survival outcomes of early‐stage non‐small‐cell lung cancer. Issue 12 (7th November 2018)

• Record Type: Journal Article
• Authors: Hong, Mi Jeong; Yoo, Seung Soo; Choi, Jin Eun; Kang, Hyo‐Gyoung; Do, Sook Kyung; Lee, Jang Hyuck; Lee, Won Kee; Lee, Jaehee; Lee, Shin Yup; Cha, Seung Ick; Kim, Chang Ho; Lee, Eung Bae; Cho, Sukki; Jheon, Sanghoon; Park, Jae Yong
• Is Part Of: Cancer science. Volume 109:Issue 12(2018)
• Page Start: 3902
• Page End: 3909
• Publication Date: 2018-11-07
• Subjects: non‐small‐cell lung cancer -- polymorphism -- RegulomeDB -- rs2257609 C>T -- survival outcome; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.13814
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract : RegulomeDB is a new tool that can predict the regulatory function of genetic variants. We applied RegulomeDB in selecting putative functional variants and evaluated the relationship between these variants and survival outcomes of surgically resected non‐small‐cell lung cancer. Among the 244 variants studied, 14 were associated with overall survival ( P < 0.05) in the discovery cohort and one variant (rs2257609 C>T) was replicated in the validation cohort. In the combined analysis, rs2257609 C>T was significantly associated with worse overall and disease‐free survival under a dominant model ( P = 2 × 10 −5 and P = 0.001, respectively). rs2257609 is located in the SLC5A10 intron, but RegulomeDB predicted that this variant affected DRG2, not SLC5A10 expression. The expression level of SLC5A10 was not different with the rs2257609 genotype. However, DRG2 expression was different according to the rs2257609 genotype ( P trend = 0.03) and was significantly higher in tumor than in non‐malignant lung tissues ( P = 1 × 10 −5 ). Luciferase assay also showed higher promoter activity of DRG2 in samples with the rs2257609 T allele ( P < 0.0001). rs2257609 C>T affected DRG2 expression and, thus, influenced the prognosis of early‐stage non‐small‐cell lung cancer. This study was approved by the Institutional Review Broad of Kyungpook National University of Hospital (Approval No. KNUMC 2014‐04‐210‐003). Abstract : Variants in non‐coding DNA may affect gene expression and, thereby, the prognosis of lung cancer patients. RegulomeDB can be used to select more putative functional variants in genetic association studies. rs2257609 C>T, which exists in the intron of SLC5A10, affected DRG2 expression and the survival outcome of lung cancer.