Author/Authors :
Li, Shanshan Research Center of Clinical Medicine - Affiliated Hospital of Nantong University - Nantong, China , Yao, Dengfu Research Center of Clinical Medicine - Affiliated Hospital of Nantong University - Nantong, China , Wang, Li Department of Informatics - Affiliated Hospital of Nantong University - Nantong, China , Wu, Wei Research Center of Clinical Medicine - Affiliated Hospital of Nantong University - Nantong, China , Qiu, Liwei Research Center of Clinical Medicine - Affiliated Hospital of Nantong University - Nantong, China , Yao, Min Research Center of Clinical Medicine - Affiliated Hospital of Nantong University - Nantong, China , Yao, Ninghua Department of Oncology - Affiliated Hospital of Nantong University - Nantong, China , Yu, Dandan Department of Oncology - Affiliated Hospital of Nantong University - Nantong, China , Ni, Qichao Department of General Surgery - Affiliated Hospital of Nantong University - Nantong, China
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.
Keywords :
Hypoxia-Inducible Factor 1, alpha Subunit , Carcinoma, Hepatocellular , Gene Expression , Vascular Endothelial Growth Factor , Angiopoietin-2
