Polymorphisms in Epithelial-Mesenchymal Transition-Related Genes and the Prognosis of Surgically Treated Non-small Cell Lung Cancer

Yangki Seok; Hyo Gyoung Kang; Shin Yup Lee; Ji Yun Jeong; Jin Eun Choi; Deuk Kju Jung; Cheng Cheng Jin; Mi Jeong Hong; Sook Kyung Do; Won Kee Lee; Ji Young Park; Kyung Min Shin; Seung Soo Yoo; Jaehee Lee; Sukki Cho; Seung Ick Cha; Chang Ho Kim; Sanghoon Jheon; Eung Bae Lee; Jae Yong Park

doi:10.1245/s10434-017-6002-4

Polymorphisms in Epithelial-Mesenchymal Transition-Related Genes and the Prognosis of Surgically Treated Non-small Cell Lung Cancer

Yangki Seok, Hyo Gyoung Kang, Shin Yup Lee, Ji Yun Jeong, Jin Eun Choi, Deuk Kju Jung, Cheng Cheng Jin, Mi Jeong Hong, Sook Kyung Do, Won Kee Lee, Ji Young Park, Kyung Min Shin, Seung Soo Yoo, Jaehee Lee, Sukki Cho, Seung Ick Cha, Chang Ho Kim, Sanghoon Jheon, Eung Bae Lee, Jae Yong Park

Department of Medicine

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5 Scopus citations

Abstract

Background: This study was conducted to determine whether single-nucleotide polymorphisms (SNPs) in EMT-related genes may influence the prognosis of NSCLC after surgery. Methods: There were 88 SNPs in EMT-related genes evaluated in a discovery set of 376 patients who underwent curative surgery for NSCLC. Significantly, 14 SNPs were evaluated in a validation set of 428 patients. Luciferase assay and RT-PCR were conducted to examine functional relevance of polymorphisms. Results: Fourteen SNPs that were associated with survival outcomes in a discovery set were selected for validation. Among those, two SNPs (FOXF2 rs1711972A>C and HEYL rs784621G>A) were replicated in a validation study. In combined analysis, FOXF2 rs1711972 AC+CC genotype was associated with significantly better overall survival (OS) and disease-free survival (DFS) compared with AA genotype (adjusted hazard ratio [aHR] for OS = 0.67, 95% confidence interval [CI] 0.51–0.88, P = 0.004; and aHR for DFS = 0.77, 95% CI 0.62–0.95, P = 0.01). HEYL rs784621 AA genotype exhibited a significantly worse OS compared with GG+GA genotype (aHR for OS = 2.65, 95% CI 1.63–4.31, P = 8 × 10⁻⁵). FOXF2 rs1711972C allele had a significantly increased promoter activity than rs1711972A allele (P = 0.01), and HEYL rs784621A allele had a significantly lower promoter activity than rs784621G allele (P = 0.004). FOXF2 rs1711972A>C was significantly associated with increased FOXF2 mRNA expression. Conclusions: FOXF2 rs1711972A>C and HEYL rs784621G>A were associated with survival outcomes of surgically treated NSCLC. These SNPs may help to identify patients at high risk of poor disease outcomes.

Original language	English
Pages (from-to)	3386-3395
Number of pages	10
Journal	Annals of Surgical Oncology
Volume	24
Issue number	11
DOIs	https://doi.org/10.1245/s10434-017-6002-4
State	Published - 1 Oct 2017

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Seok, Y., Kang, H. G., Lee, S. Y., Jeong, J. Y., Choi, J. E., Jung, D. K., Jin, C. C., Hong, M. J., Do, S. K., Lee, W. K., Park, J. Y., Shin, K. M., Yoo, S. S., Lee, J., Cho, S., Cha, S. I., Kim, C. H., Jheon, S., Lee, E. B., & Park, J. Y. (2017). Polymorphisms in Epithelial-Mesenchymal Transition-Related Genes and the Prognosis of Surgically Treated Non-small Cell Lung Cancer. Annals of Surgical Oncology, 24(11), 3386-3395. https://doi.org/10.1245/s10434-017-6002-4

@article{ded467ff6a7540da9fbda2d66e60b535,

title = "Polymorphisms in Epithelial-Mesenchymal Transition-Related Genes and the Prognosis of Surgically Treated Non-small Cell Lung Cancer",

abstract = "Background: This study was conducted to determine whether single-nucleotide polymorphisms (SNPs) in EMT-related genes may influence the prognosis of NSCLC after surgery. Methods: There were 88 SNPs in EMT-related genes evaluated in a discovery set of 376 patients who underwent curative surgery for NSCLC. Significantly, 14 SNPs were evaluated in a validation set of 428 patients. Luciferase assay and RT-PCR were conducted to examine functional relevance of polymorphisms. Results: Fourteen SNPs that were associated with survival outcomes in a discovery set were selected for validation. Among those, two SNPs (FOXF2 rs1711972A>C and HEYL rs784621G>A) were replicated in a validation study. In combined analysis, FOXF2 rs1711972 AC+CC genotype was associated with significantly better overall survival (OS) and disease-free survival (DFS) compared with AA genotype (adjusted hazard ratio [aHR] for OS = 0.67, 95% confidence interval [CI] 0.51–0.88, P = 0.004; and aHR for DFS = 0.77, 95% CI 0.62–0.95, P = 0.01). HEYL rs784621 AA genotype exhibited a significantly worse OS compared with GG+GA genotype (aHR for OS = 2.65, 95% CI 1.63–4.31, P = 8 × 10−5). FOXF2 rs1711972C allele had a significantly increased promoter activity than rs1711972A allele (P = 0.01), and HEYL rs784621A allele had a significantly lower promoter activity than rs784621G allele (P = 0.004). FOXF2 rs1711972A>C was significantly associated with increased FOXF2 mRNA expression. Conclusions: FOXF2 rs1711972A>C and HEYL rs784621G>A were associated with survival outcomes of surgically treated NSCLC. These SNPs may help to identify patients at high risk of poor disease outcomes.",

author = "Yangki Seok and Kang, {Hyo Gyoung} and Lee, {Shin Yup} and Jeong, {Ji Yun} and Choi, {Jin Eun} and Jung, {Deuk Kju} and Jin, {Cheng Cheng} and Hong, {Mi Jeong} and Do, {Sook Kyung} and Lee, {Won Kee} and Park, {Ji Young} and Shin, {Kyung Min} and Yoo, {Seung Soo} and Jaehee Lee and Sukki Cho and Cha, {Seung Ick} and Kim, {Chang Ho} and Sanghoon Jheon and Lee, {Eung Bae} and Park, {Jae Yong}",

note = "Publisher Copyright: {\textcopyright} 2017, Society of Surgical Oncology.",

year = "2017",

month = oct,

day = "1",

doi = "10.1245/s10434-017-6002-4",

language = "English",

volume = "24",

pages = "3386--3395",

journal = "Annals of Surgical Oncology",

issn = "1068-9265",

publisher = "Springer New York",

number = "11",

}

Seok, Y, Kang, HG, Lee, SY, Jeong, JY, Choi, JE, Jung, DK, Jin, CC, Hong, MJ, Do, SK, Lee, WK, Park, JY, Shin, KM, Yoo, SS, Lee, J, Cho, S, Cha, SI, Kim, CH, Jheon, S, Lee, EB & Park, JY 2017, 'Polymorphisms in Epithelial-Mesenchymal Transition-Related Genes and the Prognosis of Surgically Treated Non-small Cell Lung Cancer', Annals of Surgical Oncology, vol. 24, no. 11, pp. 3386-3395. https://doi.org/10.1245/s10434-017-6002-4

TY - JOUR

T1 - Polymorphisms in Epithelial-Mesenchymal Transition-Related Genes and the Prognosis of Surgically Treated Non-small Cell Lung Cancer

AU - Seok, Yangki

AU - Kang, Hyo Gyoung

AU - Lee, Shin Yup

AU - Jeong, Ji Yun

AU - Choi, Jin Eun

AU - Jung, Deuk Kju

AU - Jin, Cheng Cheng

AU - Hong, Mi Jeong

AU - Do, Sook Kyung

AU - Lee, Won Kee

AU - Park, Ji Young

AU - Shin, Kyung Min

AU - Yoo, Seung Soo

AU - Lee, Jaehee

AU - Cho, Sukki

AU - Cha, Seung Ick

AU - Kim, Chang Ho

AU - Jheon, Sanghoon

AU - Lee, Eung Bae

AU - Park, Jae Yong

PY - 2017/10/1

Y1 - 2017/10/1

N2 - Background: This study was conducted to determine whether single-nucleotide polymorphisms (SNPs) in EMT-related genes may influence the prognosis of NSCLC after surgery. Methods: There were 88 SNPs in EMT-related genes evaluated in a discovery set of 376 patients who underwent curative surgery for NSCLC. Significantly, 14 SNPs were evaluated in a validation set of 428 patients. Luciferase assay and RT-PCR were conducted to examine functional relevance of polymorphisms. Results: Fourteen SNPs that were associated with survival outcomes in a discovery set were selected for validation. Among those, two SNPs (FOXF2 rs1711972A>C and HEYL rs784621G>A) were replicated in a validation study. In combined analysis, FOXF2 rs1711972 AC+CC genotype was associated with significantly better overall survival (OS) and disease-free survival (DFS) compared with AA genotype (adjusted hazard ratio [aHR] for OS = 0.67, 95% confidence interval [CI] 0.51–0.88, P = 0.004; and aHR for DFS = 0.77, 95% CI 0.62–0.95, P = 0.01). HEYL rs784621 AA genotype exhibited a significantly worse OS compared with GG+GA genotype (aHR for OS = 2.65, 95% CI 1.63–4.31, P = 8 × 10−5). FOXF2 rs1711972C allele had a significantly increased promoter activity than rs1711972A allele (P = 0.01), and HEYL rs784621A allele had a significantly lower promoter activity than rs784621G allele (P = 0.004). FOXF2 rs1711972A>C was significantly associated with increased FOXF2 mRNA expression. Conclusions: FOXF2 rs1711972A>C and HEYL rs784621G>A were associated with survival outcomes of surgically treated NSCLC. These SNPs may help to identify patients at high risk of poor disease outcomes.

AB - Background: This study was conducted to determine whether single-nucleotide polymorphisms (SNPs) in EMT-related genes may influence the prognosis of NSCLC after surgery. Methods: There were 88 SNPs in EMT-related genes evaluated in a discovery set of 376 patients who underwent curative surgery for NSCLC. Significantly, 14 SNPs were evaluated in a validation set of 428 patients. Luciferase assay and RT-PCR were conducted to examine functional relevance of polymorphisms. Results: Fourteen SNPs that were associated with survival outcomes in a discovery set were selected for validation. Among those, two SNPs (FOXF2 rs1711972A>C and HEYL rs784621G>A) were replicated in a validation study. In combined analysis, FOXF2 rs1711972 AC+CC genotype was associated with significantly better overall survival (OS) and disease-free survival (DFS) compared with AA genotype (adjusted hazard ratio [aHR] for OS = 0.67, 95% confidence interval [CI] 0.51–0.88, P = 0.004; and aHR for DFS = 0.77, 95% CI 0.62–0.95, P = 0.01). HEYL rs784621 AA genotype exhibited a significantly worse OS compared with GG+GA genotype (aHR for OS = 2.65, 95% CI 1.63–4.31, P = 8 × 10−5). FOXF2 rs1711972C allele had a significantly increased promoter activity than rs1711972A allele (P = 0.01), and HEYL rs784621A allele had a significantly lower promoter activity than rs784621G allele (P = 0.004). FOXF2 rs1711972A>C was significantly associated with increased FOXF2 mRNA expression. Conclusions: FOXF2 rs1711972A>C and HEYL rs784621G>A were associated with survival outcomes of surgically treated NSCLC. These SNPs may help to identify patients at high risk of poor disease outcomes.

UR - http://www.scopus.com/inward/record.url?scp=85026535424&partnerID=8YFLogxK

U2 - 10.1245/s10434-017-6002-4

DO - 10.1245/s10434-017-6002-4

M3 - Article

C2 - 28766235

AN - SCOPUS:85026535424

SN - 1068-9265

VL - 24

SP - 3386

EP - 3395

JO - Annals of Surgical Oncology

JF - Annals of Surgical Oncology

IS - 11

ER -

Polymorphisms in Epithelial-Mesenchymal Transition-Related Genes and the Prognosis of Surgically Treated Non-small Cell Lung Cancer

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