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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 11/2019

01-10-2019 | NSCLC | Translational Research and Biomarkers

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

Authors: Jang Hyuck Lee, MS, Kyung Min Shin, MD, Shin Yup Lee, MD, PhD, Mi Jeong Hong, PhD, Jin Eun Choi, PhD, Hyo-Gyoung Kang, PhD, Sook Kyung Do, MS, Won Kee Lee, PhD, Eung Bae Lee, MD, PhD, Yangki Seok, MD, PhD, Ji Yun Jeong, MD, Seung Soo Yoo, MD, PhD, Jaehee Lee, MD, PhD, Seung Ick Cha, MD, PhD, Chang Ho Kim, MD, PhD, Sukki Cho, MD, PhD, Sanghoon Jheon, MD, PhD, Young Chul Kim, MD, PhD, In Jae Oh, MD, PhD, Kook Joo Na, MD, PhD, Moon Soo Kim, MD, Jong Mog Lee, MD, Hee Chul Yang, MD, PhD, Chi Young Jung, MD, PhD, Chang Kwon Park, MD, Min Ki Lee, MD, PhD, Dong Kwan Kim, MD, PhD, Jae Yong Park, MD, PhD

Published in: Annals of Surgical Oncology | Issue 11/2019

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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.
Appendix
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Metadata
Title
Genetic Variant of Notch Regulator DTX1 Predicts Survival After Lung Cancer Surgery
Authors
Jang Hyuck Lee, MS
Kyung Min Shin, MD
Shin Yup Lee, MD, PhD
Mi Jeong Hong, PhD
Jin Eun Choi, PhD
Hyo-Gyoung Kang, PhD
Sook Kyung Do, MS
Won Kee Lee, PhD
Eung Bae Lee, MD, PhD
Yangki Seok, MD, PhD
Ji Yun Jeong, MD
Seung Soo Yoo, MD, PhD
Jaehee Lee, MD, PhD
Seung Ick Cha, MD, PhD
Chang Ho Kim, MD, PhD
Sukki Cho, MD, PhD
Sanghoon Jheon, MD, PhD
Young Chul Kim, MD, PhD
In Jae Oh, MD, PhD
Kook Joo Na, MD, PhD
Moon Soo Kim, MD
Jong Mog Lee, MD
Hee Chul Yang, MD, PhD
Chi Young Jung, MD, PhD
Chang Kwon Park, MD
Min Ki Lee, MD, PhD
Dong Kwan Kim, MD, PhD
Jae Yong Park, MD, PhD
Publication date
01-10-2019
Publisher
Springer International Publishing
Keywords
NSCLC
NSCLC
Published in
Annals of Surgical Oncology / Issue 11/2019
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-019-07614-2

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