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

Yangki Seok MD, Hyo-Gyoung Kang PhD, Shin Yup Lee MD, PhD, Ji Yun Jeong MD, Jin Eun Choi PhD, Deuk Kju Jung PhD, Cheng Cheng Jin MD, PhD, Mi Jeong Hong PhD, Sook Kyung Do MS, Won Kee Lee PhD, Ji Young Park MD, PhD, Kyung Min Shin MD, Seung Soo Yoo MD, PhD, Jaehee Lee MD, PhD, Sukki Cho MD, PhD, Seung Ick Cha MD, PhD, Chang Ho Kim MD, PhD, Sanghoon Jheon MD, PhD, Eung Bae Lee MD, PhD, Jae Yong Park
Thoracic Oncology
Volume 24, Issue 11 / October , 2017



This study was conducted to determine whether single-nucleotide polymorphisms (SNPs) in EMT-related genes may influence the prognosis of NSCLC after surgery.


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.


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.


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.

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