Expression characteristics of HIF-1α and its clinical values in diagnosis and prognosis of hepatocellular carcinoma

Background: hypoxia-inducible factor-1 (hif-1) is a ubiquitously expressed oxygen-regulated transcription factor composed of α and β subunits. hif-1 activates the transcription of various genes including those involved in the formation and metastatic growth of hepatocellular carcinoma (hcc).objectives: to investigate the levels of hepatic and circulating hif-1? expression in a range of patients with liver disease in order to determine how it can be used in the diagnosis of hcc and in establishing prognosis.patients and methods: total rna was extracted from a self-controlled hcc and paracancerous specimen. hif-1? mrna was amplified by nested rt-pcr and confirmed by sequencing. tissue hif-1? was analyzed by immunohistochemistry. the levels of hif-1?, vascular endothelial growth factor (vegf), and angiopoietin-2 (ang-2) expression in the sera of 220 patients with liver disease were quantitatively detected by elisa.results: the positive staining of liver hif-1? was brown and granule-like and was mainly present in the cytoplasm, with lower levels in the nucleus of hepatocytes. its incidence was 80% in hcc cells and 100% in paracancerous tissues, with no significant difference in hif-1? expression in relation to tumor number, degree of differentiation, or hepatitis b surface antigen (hbsag) positivity, but with some correlation between hif-1? and tumor size. hif-1? expression was detected in the sera of hcc patients at a significantly higher level than in cases of benign liver disease, with pathological characteristics associated with the levels of circulating vegf and ang-2 expression, the size of the tumor, and the level of extrahepatic metastasis, but not with patients' gender, age, or alpha-fetoprotein (afp) levels.conclusions: hepatic hif-1? expression is associated with the development and prognosis of hcc, and circulating hif-1? level is a useful marker for hcc diagnosis and prognosis.