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

  • Thoracic Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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.

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Acknowledgment

This study was supported in part by the R&D program of MKE/KEIT (10040393, Development and commercialization of molecular diagnostic technologies for lung cancer through clinical validation), in part by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant number: HI14C0402).

Disclosures

The authors declare that they have no conflicts of interest.

Author information

Author notes

  1. Yangki Seok, Hyo-Gyoung Kang and Shin Yup Lee have contributed equally to this work.

Authors and Affiliations

  1. Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea

    Yangki Seok MD, Shin Yup Lee MD, PhD, Seung Soo Yoo MD, PhD, Eung Bae Lee MD, PhD & Jae Yong Park MD, PhD

  2. Department of Thoracic Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

    Yangki Seok MD & Eung Bae Lee MD, PhD

  3. Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

    Hyo-Gyoung Kang PhD, Jin Eun Choi PhD, Deuk Kju Jung PhD, Cheng Cheng Jin MD, PhD, Mi Jeong Hong PhD, Sook Kyung Do MS & Jae Yong Park MD, PhD

  4. Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

    Hyo-Gyoung Kang PhD, Jin Eun Choi PhD & Jae Yong Park MD, PhD

  5. Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

    Shin Yup Lee MD, PhD, Seung Soo Yoo MD, PhD, Jaehee Lee MD, PhD, Seung Ick Cha MD, PhD, Chang Ho Kim MD, PhD & Jae Yong Park MD, PhD

  6. Department of Pathology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

    Ji Yun Jeong MD & Ji Young Park MD, PhD

  7. BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea

    Deuk Kju Jung PhD, Cheng Cheng Jin MD, PhD, Mi Jeong Hong PhD, Sook Kyung Do MS & Jae Yong Park MD, PhD

  8. Biostatistics Medical Research Collaboration Center, Kyungpook National University Hospital and Kyungpook National University School of Medicine, Daegu, Republic of Korea

    Won Kee Lee PhD

  9. Department of Radiology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

    Kyung Min Shin MD

  10. Department of Thoracic and Cardiovascular Surgery, Seoul National University School of Medicine, Seoul, Republic of Korea

    Sukki Cho MD, PhD & Sanghoon Jheon MD, PhD

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  1. Yangki Seok MD
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Corresponding authors

Correspondence to Eung Bae Lee MD, PhD or Jae Yong Park MD, PhD.

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Seok, Y., Kang, HG., Lee, S.Y. et al. Polymorphisms in Epithelial-Mesenchymal Transition-Related Genes and the Prognosis of Surgically Treated Non-small Cell Lung Cancer. Ann Surg Oncol 24, 3386–3395 (2017). https://doi.org/10.1245/s10434-017-6002-4

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  • DOI: https://doi.org/10.1245/s10434-017-6002-4

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