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ABSTRACT: 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-1α 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-1α mRNA was amplified by nested RT-PCR and confirmed by sequencing. Tissue HIF-1α was analyzed by immunohistochemistry. The levels of HIF-1α, 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-1α 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-1α expression in relation to tumor number, degree of differentiation, or hepatitis B surface antigen (HBsAg) positivity, but with some correlation between HIF-1α and tumor size. HIF-1α 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-1α expression is associated with the development and prognosis of HCC, and circulating HIF-1α level is a useful marker for HCC diagnosis and prognosis.
SUBMITTER: Li S
PROVIDER: S-EPMC3234574 | biostudies-literature | 2011 Oct
REPOSITORIES: biostudies-literature
Hepatitis monthly 20111001 10
<h4>Background</h4>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).<h4>Objectives</h4>To investigate the levels of hepatic and circulating HIF-1α expression in a range of patients with liver disease in order to determine how it can be used in the diagnosis of HCC and ...[more]