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

Jang Hyuck Lee; Kyung Min Shin; Shin Yup Lee; 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 Park

doi:10.1245/s10434-019-07614-2

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

Jang Hyuck Lee, Kyung Min Shin, Shin Yup Lee, 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 NaMoon Soo Kim, Jong Mog Lee, Hee Chul Yang, Chi Young Jung, Chang Kwon Park, Min Ki Lee, Dong Kwan Kim, Jae Yong Park

Department of Medicine

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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 (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.

Original language	English
Pages (from-to)	3756-3764
Number of pages	9
Journal	Annals of Surgical Oncology
Volume	26
Issue number	11
DOIs	https://doi.org/10.1245/s10434-019-07614-2
State	Published - 1 Oct 2019

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10.1245/s10434-019-07614-2

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Lee, J. H., Shin, K. M., Lee, S. Y., Hong, M. J., Choi, J. E., Kang, H. G., Do, S. K., Lee, W. K., Lee, E. B., Seok, Y., Jeong, J. Y., Yoo, S. S., Lee, J., Cha, S. I., Kim, C. H., Cho, S., Jheon, S., Kim, Y. C., Oh, I. J., ... Park, J. Y. (2019). Genetic Variant of Notch Regulator DTX1 Predicts Survival After Lung Cancer Surgery. Annals of Surgical Oncology, 26(11), 3756-3764. https://doi.org/10.1245/s10434-019-07614-2

@article{9cd77b822d6d47a99d3722b60c8ec178,

title = "Genetic Variant of Notch Regulator DTX1 Predicts Survival After Lung Cancer Surgery",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2019, Society of Surgical Oncology.",

year = "2019",

month = oct,

day = "1",

doi = "10.1245/s10434-019-07614-2",

language = "English",

volume = "26",

pages = "3756--3764",

journal = "Annals of Surgical Oncology",

issn = "1068-9265",

publisher = "Springer Science and Business Media Deutschland GmbH",

number = "11",

}

Lee, JH, Shin, KM, Lee, SY, Hong, MJ, Choi, JE, Kang, HG, Do, SK, Lee, WK, Lee, EB, Seok, Y, Jeong, JY, Yoo, SS, Lee, J, Cha, SI, Kim, CH, Cho, S, Jheon, S, Kim, YC, Oh, IJ, Na, KJ, Kim, MS, Lee, JM, Yang, HC, Jung, CY, Park, CK, Lee, MK, Kim, DK & Park, JY 2019, 'Genetic Variant of Notch Regulator DTX1 Predicts Survival After Lung Cancer Surgery', Annals of Surgical Oncology, vol. 26, no. 11, pp. 3756-3764. https://doi.org/10.1245/s10434-019-07614-2

TY - JOUR

T1 - Genetic Variant of Notch Regulator DTX1 Predicts Survival After Lung Cancer Surgery

AU - Lee, Jang Hyuck

AU - Shin, Kyung Min

AU - Lee, Shin Yup

AU - Hong, Mi Jeong

AU - Choi, Jin Eun

AU - Kang, Hyo Gyoung

AU - Do, Sook Kyung

AU - Lee, Won Kee

AU - Lee, Eung Bae

AU - Seok, Yangki

AU - Jeong, Ji Yun

AU - Yoo, Seung Soo

AU - Lee, Jaehee

AU - Cha, Seung Ick

AU - Kim, Chang Ho

AU - Cho, Sukki

AU - Jheon, Sanghoon

AU - Kim, Young Chul

AU - Oh, In Jae

AU - Na, Kook Joo

AU - Kim, Moon Soo

AU - Lee, Jong Mog

AU - Yang, Hee Chul

AU - Jung, Chi Young

AU - Park, Chang Kwon

AU - Lee, Min Ki

AU - Kim, Dong Kwan

AU - Park, Jae Yong

PY - 2019/10/1

Y1 - 2019/10/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85068974217&partnerID=8YFLogxK

U2 - 10.1245/s10434-019-07614-2

DO - 10.1245/s10434-019-07614-2

M3 - Article

C2 - 31313037

AN - SCOPUS:85068974217

SN - 1068-9265

VL - 26

SP - 3756

EP - 3764

JO - Annals of Surgical Oncology

JF - Annals of Surgical Oncology

IS - 11

ER -

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

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