Prognostic significance of hypoxia-inducible factor-1 , TWIST1 and Snail expression in resectable non-small cell lung cancer
Open accessAbstract
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 1alpha (HIF-1alpha) promotes metastasis through regulation of certain EMT regulators. The aim of this study was to evaluate the prognostic value of HIF-1alpha, 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-1alpha, TWIST1 and Snail expression. The association between HIF-1alpha, TWIST1 and Snail expression and patients' overall and recurrence-free survivals was investigated. RESULTS: Overexpression of HIF-1alpha, TWIST1 or Snail was shown in 32.2%, 36.8% and 55.2% of primary tumours, respectively. Overexpression of HIF-1alpha, 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-1alpha was associated with a shorter recurrence-free survival (p = 0.016). We categorised the patients into four groups according to the positivity of HIF-1alpha/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-1alpha, TWIST1 and Snail is a significant prognostic predictor in patients with NSCLC.
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HIF-1 is overexpressed in 30-62% of NSCLC and 43-46% of SCLC cases, and this overexpression has been linked to worse overall survival.
“HIF-1 is overexpressed in 30 to 62% of NSCLC and 43 to 46% of SCLC cases, and its overexpression has been associated with poorer overall survival.10 –15”
From Treatment with HIF-1α Antagonist PX-478 Inhibits Progression and Spread of Orthotopic Human Small Cell Lung Cancer and Lung Adenocarcinoma in Mice (2010) · cites this paper as [13]
The resectable-NSCLC results report HIF-1α overexpression in 32.2% of 87 tumours, within the claimed NSCLC range, and associate it with shorter overall survival (p = 0.005). The paper does not establish the full 30–62% NSCLC range or address the claimed 43–46% prevalence in SCLC. Page numbers were not provided for these passages. (LLM, conf=0.88)
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- Authors
- Hung, J.-J., Yang, M.-H., Hsu, H.-S., Hsu, W.-H., Liu, J.-S., & Wu, K.-J.
- Affiliations
- Fu Jen Catholic University (TW)
- Taipei Veterans General Hospital (TW)
- Corresponding author
- Wu, K-J
- Venue
- Thorax
- Publisher
- BMJ
- Published
- 2009-09-23
- Volume
- 64
- Issue
- 12
- Pages
- 1082-1089
- ISSN
- 0040-6376 (ISSN-L)
- OpenAlex
- W2153223436
- Cited by
- 207
- References
- 36
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 5 · 2021: 8 · 2020: 15 · 2019: 12 · 2018: 11 · 2017: 17 · 2016: 14 · 2015: 16 · 2014: 20 · 2013: 27 · 2012: 15
- FWCI
- 7.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Thorax (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Science Council
- Cathay General Hospital
- National Health Research Institutes
- Taipei Veterans General Hospital
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Keywords
- non-small cell lung cancer, hypoxia-inducible factor-1α, TWIST1, snails, epithelial-mesenchymal transition, intratumoral hypoxia, prognostic factors, metastasis, overall survival, recurrence-free survival, surgical resection
- MeSH terms
- Snail Family Transcription Factors, Aged, Carcinoma, Non-Small-Cell Lung, Epidemiologic Methods, Female, Humans, Lung Neoplasms, Male, Middle Aged, Neoplasm Proteins, Neoplasm Staging, Nuclear Proteins, Prognosis, Transcription Factors, Biomarkers, Tumor, Treatment Outcome, Chemotherapy, Adjuvant, Hypoxia-Inducible Factor 1, alpha Subunit, Twist-Related Protein 1
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