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Ann Surg Oncol. 2017 Oct;24(11):3386-3395. doi: 10.1245/s10434-017-6002-4. Epub 2017 Aug 1.

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

Seok Y1,2, Kang HG3,4, Lee SY1,5, Jeong JY6, Choi JE3,4, Jung DK3,7, Jin CC3,7, Hong MJ3,7, Do SK3,7, Lee WK8, Park JY6, Shin KM9, Yoo SS1,5, Lee J5, Cho S10, Cha SI5, Kim CH5, Jheon S10, Lee EB11,12, Park JY13,14,15,16,17.

Author information

1
Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.
2
Department of Thoracic Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
3
Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
4
Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
5
Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
6
Department of Pathology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
7
BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea.
8
Biostatistics Medical Research Collaboration Center, Kyungpook National University Hospital and Kyungpook National University School of Medicine, Daegu, Republic of Korea.
9
Department of Radiology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
10
Department of Thoracic and Cardiovascular Surgery, Seoul National University School of Medicine, Seoul, Republic of Korea.
11
Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea. bay@knu.ac.kr.
12
Department of Thoracic Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. bay@knu.ac.kr.
13
Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea. jaeyong@knu.ac.kr.
14
Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. jaeyong@knu.ac.kr.
15
Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. jaeyong@knu.ac.kr.
16
Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. jaeyong@knu.ac.kr.
17
BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea. jaeyong@knu.ac.kr.

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.

PMID:
28766235
DOI:
10.1245/s10434-017-6002-4
[Indexed for MEDLINE]

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