Clinical significance of hypoxia-inducible factor-1a messenger RNA expression in locally advanced non-small-cell lung cancer after platinum agent and gemcitabine chemotherapy followed by surgery

Clin Lung Cancer. 2005 Mar;6(5):299-303. doi: 10.3816/clc.2005.n.009.

Abstract

Hypoxia-inducible factor-1a (HIF-1a) is a key regulator of the angiogenic cascade. This study analyzed HIF-1a messenger RNA expression levels using real-time quantitative polymerase chain reaction (PCR) in paraffin-embedded surgical specimens from 54 stage IIB-III patients with non-small-cell lung cancer (NSCLC) treated with induction platinum/gemcitabine followed by surgery between September 1998 and December 2002. Radiographic response was observed in 61% of patients. Median survival was 37.8 months. Forty-five patients with complete resection attained a 52-month median survival, whereas 8 patients with incomplete resection had a 12-month median survival, and 1 unresectable patient had a survival of 14 months. No significant differences were observed in overall survival (OS) or event-free survival (EFS) according to HIF-1a expression levels. Patients were divided into quartiles according to HIF-1a gene expression levels. Median EFS for the 13 patients in the lowest quartile has not been reached yet, whereas median EFS for the 13 patients in the top quartile was 9 months (P = 0.192). Similarly, median OS for the 13 patients in the lowest quartile has not been reached yet, whereas median OS for the 13 patients in the top quartile was 52 months (P = 0.297). The cisplatin/gemcitabine combination is highly active in neoadjuvant treatment. Hypoxia-inducible factor-1a expression levels analyzed by real-time quantitative PCR in surgery specimens after platinum/gemcitabine therapy do not correlate with the outcome of patients with stage II/III NSCLC.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Carboplatin / administration & dosage
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Cisplatin / administration & dosage
  • DNA-Binding Proteins / biosynthesis*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Female
  • Gemcitabine
  • Gene Expression / physiology
  • Humans
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Staging
  • Nuclear Proteins / biosynthesis*
  • Pneumonectomy
  • RNA, Messenger / biosynthesis
  • Survival Analysis
  • Transcription Factors / biosynthesis*
  • Treatment Outcome

Substances

  • DNA-Binding Proteins
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Nuclear Proteins
  • RNA, Messenger
  • Transcription Factors
  • Deoxycytidine
  • Carboplatin
  • Cisplatin
  • Gemcitabine