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Prognostic value of Iroquois homeobox 1 methylation in non-small cell lung cancers

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Abstract

Background

Non-small cell lung cancer (NSCLC) poses a great threat to human health. DNA methylation abnormalities play a central role in the development and outcome of most human malignancies, providing potential biomarkers for diagnosis and prognosis. Iroquois homeobox 1 (IRX1) can act as a tumor suppressor or promoter depending on the tumor microenvironment, and its role in lung cancer is still controversial.

Objective

The purpose of this study was to investigate the biological role and prognostic value of IRX1 in NSCLC.

Methods

We examined the methylation status of IRX1 promoter in 146 tumors from patients with NSCLC using pyrosequencing and analyzed the association between methylation status and overall patient survival.

Results

A total of 37 cases (25.3%) showed IRX1 methylation-positive tumors when compared with matched normal tissues. No association between IRX1 expression level and methylation status was found in lung cancer cell lines. IRX1 methylation significantly correlated with smoking status and TP53 mutation. Patients with IRX1 methylation showed significantly longer survival than patients without methylation (log-rank P = 0.011). In a multivariate analysis of prognostic factors, IRX1 methylation in tumor samples was an independent prognostic factor (adjusted hazard ratio = 0.35, 95% confidence interval 0.17–0.73, P = 0.005).

Conclusion

These results suggest that IRX1 promoter methylation may be a tumor-associated event and an independent predictor of survival advantage in patients with NSCLC. Further large-scale studies are needed to confirm these findings.

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Funding

This study was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) (No. NRF-2016R1D1A1B03931462).

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Authors and Affiliations

  1. Department of Anatomy and BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, 2-101 Dongin-dong, Jung-gu, Daegu, 702-422, Republic of Korea

    Ji Yun Lee & Dong Sun Kim

  2. Department of Preventive Medicine, School of Medicine, Kyungpook National University, Daegu, 702-422, Republic of Korea

    Won Kee Lee

  3. Department of Internal Medicine, School of Medicine, Kyungpook National University, 2-101 Dongin-dong, Jung-gu, Daegu, 702-422, Republic of Korea

    Jae Yong Park

Authors
  1. Ji Yun Lee
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  2. Won Kee Lee
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  4. Dong Sun Kim
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Contributions

JYL contributed to the experimental design and implementation, performed the experiments and data analysis, and drafted the manuscript. LWK performed statistical analyses. PJY and KDS contributed to experiment implementation, interpreted the patient data and modified the manuscript. All authors have read and approved the final manuscript.

Corresponding authors

Correspondence to Jae Yong Park or Dong Sun Kim.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the Ethics Committee of KNUHl (No. 2014-04-210).

Informed consent

Written informed consent was obtained from all participants or their families prior to obtaining the samples.

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Lee, J.Y., Lee, W.K., Park, J.Y. et al. Prognostic value of Iroquois homeobox 1 methylation in non-small cell lung cancers. Genes Genom 42, 571–579 (2020). https://doi.org/10.1007/s13258-020-00925-9

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  • DOI: https://doi.org/10.1007/s13258-020-00925-9

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