Genetic Variant of Notch Regulator DTX1 Predicts Survival After Lung Cancer Surgery
- Authors
- Lee, Jang Hyuck; Shin, Kyung Min; Lee, Shin Yup; Hong, Mi Jeong; Choi, Jin Eun; Kang, Hyo-Gyoung; Do, Sook Kyung; Lee, Won Kee; Lee, Eung Bae; Seok, Yangki; Jeong, Ji Yun; Yoo, Seung Soo; Lee, Jaehee; Cha, Seung Ick; Kim, Chang Ho; Cho, Sukki; Jheon, Sanghoon; Kim, Young Chul; Oh, In Jae; Na, Kook Joo; Kim, Moon Soo; Lee, Jong Mog; Yang, Hee Chul; Jung, Chi Young; Park, Chang Kwon; Lee, Min Ki; Kim, Dong Kwan; Park, Jae Yong
- Issue Date
- Oct-2019
- Publisher
- Lippincott Williams & Wilkins Ltd.
- Keywords
- DTX1; lung cancer; survival
- Citation
- Annals of Surgical Oncology, v.26, no.11, pp 3756 - 3764
- Pages
- 9
- Journal Title
- Annals of Surgical Oncology
- Volume
- 26
- Number
- 11
- Start Page
- 3756
- End Page
- 3764
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/4196
- DOI
- 10.1245/s10434-019-07614-2
- ISSN
- 1068-9265
1534-4681
- Abstract
- Background We evaluated the association between genetic variants in the Notch pathway and survival outcomes of patients with surgically resected NSCLC. Methods Sixty-four single nucleotide polymorphisms (SNPs) in the Notch pathway genes were evaluated in the discovery study (n = 354) and two sequential validation studies (n = 772 and n = 746, respectively). The association of genotype with overall survival (OS) and disease-free survival (DFS) was evaluated. Results Of the 64 SNPs analyzed in the discovery study, 9 were significantly associated with OS or DFS. Among them, the association remained significant only for Deltex-1 (DTX1) rs1732786A>G in the first validation study. The second validation study confirmed again the association between DTX1 rs1732786A>G and survival outcomes. In the combined analysis, rs1732786A>G was significantly associated with better OS and DFS (adjusted HR center dot aHR center dot for OS, 0.75; 95% CI 0.64-0.87; P = 0.0002; aHR for DFS, 0.79; 95% CI 0.71-0.89; P = 0.0001). In vitro luciferase assay showed that the rs1732786G allele was associated with higher promoter activity compared to rs1732786A allele. Consistently, relative mRNA expression level of DTX1 showed significant positive correlation with rs1732786 A-to-G change (P-trend = 0.02) in tumor tissues. Conclusions These results suggest that DTX1 rs1732786 is a potential prognostic factor that may have clinical utility in the management of early stage NSCLC.
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Collections - College of Medicine > Department of Cardiovascula Surgery > 1. Journal Articles
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