Research Article

Epigenetic inactivation of Homeobox A5 gene in nonsmall cell lung cancer and its relationship with clinicopathological features

  1. Dong-Sun Kim1,
  2. Min-Jin Kim1,
  3. Ji-Yun Lee1,
  4. Su-Man Lee1,
  5. Jun-Young Choi1,
  6. Ghil-Suk Yoon2,
  7. Yeon-Kyung Na3,
  8. Hae-Sook Hong3,
  9. Sang-Geol Kim4,
  10. Jin-Eun Choi5,
  11. Shin-Yeop Lee5,
  12. Jae-Yong Park5,*

Article first published online: 24 JUN 2009

DOI: 10.1002/mc.20561

Issue

Molecular Carcinogenesis

Molecular Carcinogenesis

Volume 48, Issue 12, pages 1109–1115, December 2009

Additional Information

How to Cite

Kim, D.-S., Kim, M.-J., Lee, J.-Y., Lee, S.-M., Choi, J.-Y., Yoon, G.-S., Na, Y.-K., Hong, H.-S., Kim, S.-G., Choi, J.-E., Lee, S.-Y. and Park, J.-Y. (2009), Epigenetic inactivation of Homeobox A5 gene in nonsmall cell lung cancer and its relationship with clinicopathological features. Molecular Carcinogenesis, 48: 1109–1115. doi: 10.1002/mc.20561

Author Information

  1. 1

    Department of Anatomy, Kyungpook National University, Daegu, Republic of Korea

  2. 2

    Department of Pathology, Kyungpook National University, Daegu, Republic of Korea

  3. 3

    College of Nursing, Kyungpook National University, Daegu, Republic of Korea

  4. 4

    Department of General Surgery, Kyungpook National University, Daegu, Republic of Korea

  5. 5

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

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

Publication History

  1. Issue published online: 23 NOV 2009
  2. Article first published online: 24 JUN 2009
  3. Manuscript Accepted: 18 MAY 2009
  4. Manuscript Revised: 6 MAY 2009
  5. Manuscript Received: 7 OCT 2008

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Keywords:

  • HOXA5;
  • methylation;
  • NSCLC

Abstract

Promoter methylation is an important mechanism in gene silencing and is a key epigenetic event in cancer development. Homeobox A5 (HOXA5) is a master regulator of the morphogenesis and cell differentiation to be implicated as a tumor suppressor gene in breast cancer, but its role in lung cancer is still unknown. In this study, we have investigated the methylation status of the promoter region of the HOXA5 gene in nonsmall cell lung cancers (NSCLCs) using nested and standard methylation-specific PCR (MSP) and correlated the methylation status with clinicopathological features. With standard MSP analysis, HOXA5 methylation were found in 113 (81.3%) of 139 NSCLCs and 72 (51.8%) in their corresponding nonmalignant lung tissues. RT-PCR and immunohistochemical analysis showed that HOXA5 methylation correlates with gene expression. Moreover, in the patients with stage I disease, HOXA5 methylation was more frequent in smokers than in never-smokes (P = 0.01). There was no influence of HOXA5 methylation on survival in all NSCLCs or at stages II–IV. However, in the patients with stage I disease, HOXA5 methylation was associated with a borderline significantly worse survival (P = 0.09). These findings suggest that downregulation of the HOXA5 gene by aberrant promoter methylation occurs in the vast majority of NSCLCs and that it may play a role in the pathogenesis of NSCLC. Additional studies with larger sample sizes are required to evaluate the prognostic value of HOXA5 methylation in patients with stage I NSCLC. © 2009 Wiley-Liss, Inc.

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