Independent Prognostic Value of Hypoxia-inducible Factor 1-alpha Expression in Small Cell Lung Cancer

Int J Med Sci. 2017 Jul 18;14(8):785-790. doi: 10.7150/ijms.19512. eCollection 2017.

Abstract

Hypoxia is an important factor in tumor angiogenesis, metastasis, and resistance to chemotherapy or radiotherapy, and may be an indicator of poor prognosis. The transcription factor hypoxia-inducible factor 1 (HIF-1) is the key regulator of the hypoxic state. This study was designed to evaluate the prognostic value of HIF-1α expression in small cell lung cancer (SCLC). Forty-three paraffin-embedded biopsy materials were examined using immunohistochemistry. Our results indicated that the expression of HIF-1α was high in males, and patients with poor Eastern Cooperative Oncology Group (ECOG) performance status and metastases. To elucidate the prognostic value of HIF-1α expression, Kaplan-Meier analysis was carried out and the results showed that patients with high HIF-1α expression had a poorer prognosis than patients with low expression of HIF-1α. After adjusting clinical parameters by the Cox proportional hazards model, our results demonstrated that high HIF-1α expression is an independent prognostic factor for SCLC with a 39.2-fold risk of death (p<0.003). In conclusion, we have provided evidence that HIF-1α expression has significant value in predicting survival of patients with SCLC and is an independent prognostic factor beyond ECOG performance and metastasis status.

Keywords: hypoxia-inducible factor-1 alpha; immunohistochemistry; small cell lung cancer; survival.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neovascularization, Pathologic / diagnosis
  • Neovascularization, Pathologic / genetics*
  • Neovascularization, Pathologic / pathology
  • Prognosis
  • Proportional Hazards Models
  • Small Cell Lung Carcinoma / genetics*
  • Small Cell Lung Carcinoma / mortality
  • Small Cell Lung Carcinoma / pathology

Substances

  • Biomarkers, Tumor
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit