Expression Characteristics of Hypoxia-Inducible Factor-1α and Its Clinical Values in Diagnosis and Prognosis of Hepatocellular Carcinoma

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. Implication for health policy/practice/research/medical education:HCC is a global health problem and one of the common fatal malignancies associated with the highest incidence in patients with chronic hepatitis and liver cirrhosis. The current study tries to explore HIF-1α expression and trans- activates various genes related to HCC aggressiveness. Therefore, the study may recommend for researchers in the field of public health, diagnosis and prognosis of HCC. Please cite this paper as:Li S, Yao D, Wang L, Wu W, Qiu L, Yao M, et al. Expression Characteristics of Hypoxia-Inducible Factor-1α and Its Clinical Values in Diagnosis and Prognosis of Hepatocellular Carcinoma. Hepat Mon. 2011;11(10):821-8. DOI: 10.5812/kowsar.1735143X.771. © 2011 Kowsar M.P.Co. All rights reserved.