aHIF but not HIF-1α transcript is a poor prognostic marker in human breast cancer

Background: Hypoxia-inducible factor-1alpha (HIF-1alpha) is part of a transcriptional factor that regulates genes involved in metabolic and vascular adaptation of tumours to oxygen restriction. A splicing variant lacking exon 14 (sHIF-1alpha) encodes a truncated protein that competes with the normal HIF-1alpha protein, decreasing its activity. A natural antisense transcript (aHIF) complementary to the 3'-untranslated region of HIF-1alpha mRNA was described recently. Methods: With a semiquantitative multiplex reverse transcriptase-PCR (RT-PCR) assay, we assessed transcript concentrations of HIF-1alpha, sHIF-1alpha and aHIF in 110 patients with invasive breast carcinoma. Results: We found a strong positive association between HIF-1alpha and sHIF-1alpha, sHIF-1alpha and aHIF, and an inverse correlation between HIF-1alpha/sHIF-1alpha and aHIF. aHIF transcript expression was associated with poor disease-free survival in univariate (P=0.0038) and multivariate (P=0.0016) analyses in this series of high-risk primary breast carcinomas. Conclusion: In our series of breast cancer patients, aHIF, and not HIF-1alpha transcript, is a marker of poor prognosis.