Genetic Variant of Notch Regulator DTX1 Predicts Survival After Lung Cancer Surgery.

Autor: Lee JH; Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Korea.; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Korea., Shin KM; Department of Radiology, School of Medicine, Kyungpook National University, Daegu, Korea., Lee SY; Lung Cancer Center, Kyungpook National University Chilgok Hospital, 807, Hoguk-ro, Buk-gu, Daegu, 41404, Korea. shinyup@knu.ac.kr.; Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea. shinyup@knu.ac.kr., Hong MJ; Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Korea.; Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea., Choi JE; Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Korea.; Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea., Kang HG; Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Korea.; Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea., Do SK; Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Korea.; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Korea., Lee WK; Medical Research Collaboration Center in Kyungpook National University Hospital and School of Medicine, Kyungpook National University, Daegu, Korea., Lee EB; Lung Cancer Center, Kyungpook National University Chilgok Hospital, 807, Hoguk-ro, Buk-gu, Daegu, 41404, Korea.; Department of Thoracic Surgery, School of Medicine, Kyungpook National University, Daegu, Korea., Seok Y; Lung Cancer Center, Kyungpook National University Chilgok Hospital, 807, Hoguk-ro, Buk-gu, Daegu, 41404, Korea.; Department of Thoracic Surgery, Soonchunhyang University Gumi Hospital, Gumi, Korea., Jeong JY; Department of Pathology, School of Medicine, Kyungpook National University, Daegu, Korea., Yoo SS; Lung Cancer Center, Kyungpook National University Chilgok Hospital, 807, Hoguk-ro, Buk-gu, Daegu, 41404, Korea.; Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea., Lee J; Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea., Cha SI; Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea., Kim CH; Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea., Cho S; Department of Thoracic and Cardiovascular Surgery, Seoul National University School of Medicine, Seoul, Korea., Jheon S; Department of Thoracic and Cardiovascular Surgery, Seoul National University School of Medicine, Seoul, Korea., Kim YC; Department of Internal Medicine, Chonnam National University Hwasun Hospital, Hwasun-gun, Jeollanam-do, Korea., Oh IJ; Department of Internal Medicine, Chonnam National University Hwasun Hospital, Hwasun-gun, Jeollanam-do, Korea., Na KJ; Department of Thoracic and Cardiovascular Surgery, Chonnam National University Hwasun Hospital, Hwasun-gun, Jeollanam-do, Korea., Kim MS; Center for Lung Cancer, National Cancer Center, Goyang, Korea., Lee JM; Center for Lung Cancer, National Cancer Center, Goyang, Korea., Yang HC; Center for Lung Cancer, National Cancer Center, Goyang, Korea., Jung CY; Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea., Park CK; Department of Thoracic and Cardiovascular Surgery, Keimyung University School of Medicine, Daegu, Korea., Lee MK; Department of Internal Medicine, Pusan National University School of Medicine, Busan, South Korea., Kim DK; Department of Thoracic and Cardiovascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea., Park JY; Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Korea. jaeyong@knu.ac.kr.; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Korea. jaeyong@knu.ac.kr.; Lung Cancer Center, Kyungpook National University Chilgok Hospital, 807, Hoguk-ro, Buk-gu, Daegu, 41404, Korea. jaeyong@knu.ac.kr.; Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea. jaeyong@knu.ac.kr.; Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea. jaeyong@knu.ac.kr.
Jazyk: angličtina
Zdroj: Annals of surgical oncology [Ann Surg Oncol] 2019 Oct; Vol. 26 (11), pp. 3756-3764. Date of Electronic Publication: 2019 Jul 16.
DOI: 10.1245/s10434-019-07614-2
Abstrakt: 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 ·aHR· 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.
Databáze: MEDLINE
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