Prognostic value of hypoxia-induced factor 2a in circulating cancer cell in patients with hepatocellular carcinoma after radiofrequency ablation

Abstract

BACKGROUND: Tumor hypoxia leads to more aggressive tumor behaviour in terms of recurrence and metastasis. Over-expression of hypoxia inducible transcription factor (HIF) complexes is associated with high mortality and treatment failure rates in various cancers. However, the significance of circulating cancer cells expressing HIF-2α in patients with hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) treatment has not been studied. AIM OF STUDY: This study is to evaluate the prognostic value of HIF-2α in circulating cancer cells in patients with HCC after RFA. PATIENTS AND METHODS: From August 2001 to December 2005, samples of blood cell pellet were collected from 38 patients with HCC receiving RFA as primary treatment modality. Quantitative real-time polymerase chain reaction was performed to detect HIF-2α at mRNA level before and 7 days after treatment. Blood cell pellet samples from 12 normal subjects and 10 patients with cirrhosis served as controls. Correlation between HIF-2α level and disease-free survival of HCC patients was analyzed. RESULTS: Forty-seven tumor nodules in 38 patients were treated by RFA with curative intent. Complete ablation rate was 92%. With median follow-up period of 36 months, the local, intrahepatic and distant recurrence rates were 9.4%, 63.1% and 50%, respectively. There were up-regulations of HIF-2α at mRNA level in HCC patients before RFA when compared with normal objects and cirrhotic patients. This provided the evidence of circulating cancer cells expressing HIF-2α in patients with HCC. The role of HIF-2α was further elucidated by the positive correlation between post-RFA HIF-2α level and high tumor recurrence. Patients with high post-RFA HIF-2α level had worse disease-free survival than that of those with low HIF-2α level (1-year: 84% vs. 100%, 3-year: 56% vs. 80%, 5-year: 18% vs. 45%) (P = 0.0422). CONCLUSION: High HIF-2α at mRNA level in circulating cancer cells after radiofrequency ablation for hepatocellular carcinoma is associated with poor disease-free survival. Aggressive adjuvant therapy and close monitoring of recurrence are indicated in this subgroup of patients.