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Annals of Surgical Oncology

, Volume 26, Issue 11, pp 3756–3764 | Cite as

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

  • Jang Hyuck Lee
  • Kyung Min Shin
  • Shin Yup LeeEmail author
  • Mi Jeong Hong
  • Jin Eun Choi
  • Hyo-Gyoung Kang
  • Sook Kyung Do
  • Won Kee Lee
  • Eung Bae Lee
  • Yangki Seok
  • Ji Yun Jeong
  • Seung Soo Yoo
  • Jaehee Lee
  • Seung Ick Cha
  • Chang Ho Kim
  • Sukki Cho
  • Sanghoon Jheon
  • Young Chul Kim
  • In Jae Oh
  • Kook Joo Na
  • Moon Soo Kim
  • Jong Mog Lee
  • Hee Chul Yang
  • Chi Young Jung
  • Chang Kwon Park
  • Min Ki Lee
  • Dong Kwan Kim
  • Jae Yong ParkEmail author
Translational Research and Biomarkers
  • 63 Downloads

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 ·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 (Ptrend = 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.

Notes

Acknowledgment

This work has supported in part by the National Research Foundation of Korea (NRF) Grant funded by the Korea Government (MSIT) (No. NRF-2018R1A2B2003038), in part by the National Research Foundation of Korea (NRF) grant funded by the Korea Government (2014R1A5A2009242). The biospecimens and data used for this study were provided by National Biobank of Korea-Kyungpook National University Hospital (KNUH), a member of the KoreaBiobank Network-KNUH were obtained (with informed consent) under institutional review board (IRB)-approved protocols.

Disclosures

The authors declare no conflict of interests.

Supplementary material

10434_2019_7614_MOESM1_ESM.docx (46 kb)
Supplementary material 1 (DOCX 46 kb)
10434_2019_7614_MOESM2_ESM.pdf (95 kb)
Supplementary material 2 (PDF 95 kb)

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Copyright information

© Society of Surgical Oncology 2019

Authors and Affiliations

  • Jang Hyuck Lee
    • 1
    • 2
  • Kyung Min Shin
    • 3
  • Shin Yup Lee
    • 4
    • 5
    Email author
  • Mi Jeong Hong
    • 1
    • 6
  • Jin Eun Choi
    • 1
    • 6
  • Hyo-Gyoung Kang
    • 1
    • 6
  • Sook Kyung Do
    • 1
    • 2
  • Won Kee Lee
    • 7
  • Eung Bae Lee
    • 4
    • 8
  • Yangki Seok
    • 4
    • 9
  • Ji Yun Jeong
    • 10
  • Seung Soo Yoo
    • 4
    • 5
  • Jaehee Lee
    • 5
  • Seung Ick Cha
    • 5
  • Chang Ho Kim
    • 5
  • Sukki Cho
    • 11
  • Sanghoon Jheon
    • 11
  • Young Chul Kim
    • 12
  • In Jae Oh
    • 12
  • Kook Joo Na
    • 13
  • Moon Soo Kim
    • 14
  • Jong Mog Lee
    • 14
  • Hee Chul Yang
    • 14
  • Chi Young Jung
    • 15
  • Chang Kwon Park
    • 16
  • Min Ki Lee
    • 17
  • Dong Kwan Kim
    • 18
  • Jae Yong Park
    • 1
    • 2
    • 4
    • 5
    • 6
    Email author
  1. 1.Department of Biochemistry and Cell Biology, School of MedicineKyungpook National UniversityDaeguKorea
  2. 2.BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical ScienceKyungpook National UniversityDaeguKorea
  3. 3.Department of Radiology, School of MedicineKyungpook National UniversityDaeguKorea
  4. 4.Lung Cancer CenterKyungpook National University Chilgok HospitalDaeguKorea
  5. 5.Department of Internal Medicine, School of MedicineKyungpook National UniversityDaeguKorea
  6. 6.Cell and Matrix Research Institute, School of MedicineKyungpook National UniversityDaeguKorea
  7. 7.Medical Research Collaboration Center in Kyungpook National University Hospital and School of MedicineKyungpook National UniversityDaeguKorea
  8. 8.Department of Thoracic Surgery, School of MedicineKyungpook National UniversityDaeguKorea
  9. 9.Department of Thoracic SurgerySoonchunhyang University Gumi HospitalGumiKorea
  10. 10.Department of Pathology, School of MedicineKyungpook National UniversityDaeguKorea
  11. 11.Department of Thoracic and Cardiovascular SurgerySeoul National University School of MedicineSeoulKorea
  12. 12.Department of Internal MedicineChonnam National University Hwasun HospitalHwasun-gunKorea
  13. 13.Department of Thoracic and Cardiovascular SurgeryChonnam National University Hwasun HospitalHwasun-gunKorea
  14. 14.Center for Lung CancerNational Cancer CenterGoyangKorea
  15. 15.Department of Internal MedicineDaegu Catholic University School of MedicineDaeguKorea
  16. 16.Department of Thoracic and Cardiovascular SurgeryKeimyung University School of MedicineDaeguKorea
  17. 17.Department of Internal MedicinePusan National University School of MedicineBusanSouth Korea
  18. 18.Department of Thoracic and Cardiovascular SurgeryAsan Medical Center, University of Ulsan College of MedicineSeoulKorea

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