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  • Prognostic significance of hypoxia-inducible factor-1α, TWIST1 and Snail expression in resectable non-small cell lung cancer

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Lung cancer
Prognostic significance of hypoxia-inducible factor-1α, TWIST1 and Snail expression in resectable non-small cell lung cancer
  1. J-J Hung1,3,4,6,
  2. M-H Yang1,7,8,
  3. H-S Hsu2,6,8,
  4. W-H Hsu3,6,
  5. J-S Liu4,
  6. K-J Wu1,5,8
  1. 1
    Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
  2. 2
    Institute of Emergency and Critical Care Medicine, National Yang-Ming University, Taipei, Taiwan
  3. 3
    School of Medicine, National Yang-Ming University, Taipei, Taiwan
  4. 4
    Department of Surgery, Cathay General Hospital and School of Medicine, Fu Jen Catholic University, Taipei, Taiwan
  5. 5
    Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan
  6. 6
    Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
  7. 7
    Division of Hematology-Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
  8. 8
    Genomic Research Center, Taipei Veterans General Hospital, Taipei, Taiwan
  1. Correspondence to Dr K-J Wu, Institute of Biochemistry and Molecular Biology, National Yang-Ming University, No. 155, Section 2, Li-Nong Street, Peitou, Taipei 112, Taiwan; kjwu2{at}ym.edu.tw

Abstract

Background: Metastasis is the most common cause of disease failure and mortality for non-small cell lung cancer (NSCLC) after surgical resection. Snail and TWIST1 are epithelial-mesenchymal transition (EMT) regulators which induce metastasis. Intratumoral hypoxia followed by stabilisation of hypoxia-inducible factor 1α (HIF-1α) promotes metastasis through regulation of certain EMT regulators. The aim of this study was to evaluate the prognostic value of HIF-1α, TWIST1 and Snail expression in patients with resectable NSCLC.

Methods: A retrospective analysis of 87 patients with resectable NSCLC from Taipei Veterans General Hospital between 2003 and 2004 was performed using immunohistochemistry to analyse HIF-1α, TWIST1 and Snail expression. The association between HIF-1α, TWIST1 and Snail expression and patients’ overall and recurrence-free survivals was investigated.

Results: Overexpression of HIF-1α, TWIST1 or Snail was shown in 32.2%, 36.8% and 55.2% of primary tumours, respectively. Overexpression of HIF-1α, TWIST1 or Snail in primary NSCLCs was associated with a shorter overall survival (p = 0.005, p = 0.026, p = 0.009, respectively), and overexpression of HIF-1α was associated with a shorter recurrence-free survival (p = 0.016). We categorised the patients into four groups according to the positivity of HIF-1α/TWIST1/Snail to investigate the accumulated effects of these markers on survival. Co-expression of more than two markers was an independent prognostic indicator for both recurrence-free survival and overall survival (p = 0.004 and p<0.001, respectively, by multivariate Cox proportional hazards model).

Conclusions: Co-expression of more than two markers from HIF-1α, TWIST1 and Snail is a significant prognostic predictor in patients with NSCLC.

https://doi.org/10.1136/thx.2009.115691

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    Footnotes

    • Funding This work was supported in part by the National Science Council (NSC97-2320-B-010-029, NSC97-2311-B-010-007) (K-JW), NRPGM (DOH97-TD-G-111-038, DOH98-TD-G-111-027) (K-JW), Taipei Veterans General Hospital (97-C1-032, 97-ER2-008) (M-HY), Cathay General Hospital (CGH-MR-9711) (J-JH), a grant from the Ministry of Education, Aim for the Top University Plan (98-AC-T-509) (K-JW), National Health Research Institutes (NHRI-EX98-9611BI) (K-JW).

    • Competing interests None.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Ethics approval Informed consent was obtained in writing before patient enrolment. This study has been approved by the Institutional Review Board of Taipei Veterans General Hospital.

    • M-HY and H-SH contributed equally to this article.

    • ▸ Complete results of multivariate analyses are published online only at http://thorax.bmj.com/content/vol64/issue12