| Background:Hepatocellular carcinoma is one of the most common malignancies in the world, and its mortality rate ranks the third in cancer. China is now home to the most cases of hepatocellular carcinoma worldwide, and nearly250,000people die of this disease each year, which accounts for45percent of the global hepatocellular carcinoma death toll. Hepatocellular carcinoma may occur at any age, and show poor prognosis. If without any treatment, hepatocellular carcinoma patients will have a5-year overall survival of less than5%. Hepatocellular carcinoma is a high malignancy with insidious onset, invasive fast-growing, high recurrence and metastasis rate after treatment, high mortality. At present, the main treatment of liver cancer consists of surgery, interventional therapy, radiotherapy, chemotherapy, Chinese medicine and so on, but the overall curative effect is not so good. So it is important to study the relationship between biological characteristics of hepatocellular carcinoma and clinicopathological features. It may provide more theoretical basis and new ideas for reasonable treatment of hepatocellular carcinoma. In this study, we will apply the immunohistochemistry to detect the expressions of hypoxia-inducible factor-1α (HIF-1α) and HIF prolyl hydroxylases PHD1, PHD2and PHD3in hepatocellular carcinoma, to research the relationship between their expressions and biological characters of hepatocellular carcinoma, and to analyze the influence of the expressions on the prognosis.Objective:To explore the expressions of HIF-1α, PHD1, PHD2and PHD3in hepatocellular carcinoma, and to study the relationship between their expressions and clinicopathological characteristics of hepatocellular carcinoma, and to analyze the influence on the patients’ prognosis.Methods:(1) To collect103cases of hepatocellular carcinoma and14cases of pericarcinous tissues with complete information from December2005to December2010in Lishui central hospital of Zhejiang province. All of these cases were performed with radical resection. Another13cases with pathologically proved normal liver tissues.(2) Tissue microarray and immunohistochemical study (EnVision method) were used in testing the expression of HIF-1α, PHD1, PHD2and PHD3in the tissue microarray, which consisted of103cases of hepatocellular carcinoma,14cases of pericarcinous tissues, and13cases of normal liver tissues. All the specimens were examined immunohistochemically and divided into positive group and negative group according to the level of expression. Statistical analysis was performed using SPSS17.0, and P<0.05has the statistical significance. Results:(1) The positive expression rate of HIF-1α significantly higher in hepatocellular carcinoma (63.1%) than in paracancerous tissues (35.7%), the difference was statistically significant (P<0.05). But HIF-1α was not expressed in normal liver tissue. The positive expression of PHD1in hepatocellular carcinoma (53.4%) was much higher than that in the normal liver tissue (23.1%), the difference was statistically significant (P<0.05). But the positive expression of PHD2in hepatocellular carcinoma (56.3%) was significantly lower than that in the normal liver tissue (84.6%), the difference was statistically significant (P<0.05). The positive expression of PHD3in hepatocellular carcinoma (57.3%), was significantly higher than that in pericarcinous tissue (28.6%) and normal liver tissue (15.4%) respectively, the difference was statistically significant (P<0.05).(2) The expression of HIF-1α in hepatocellular carcinoma was significantly correlated with tumor size, tumor embolus, degree of tumor differentiation, TNM stages and the two-year survival rate after operation (P<0.05). The expression of PHD1in hepatocellular carcinoma was highly correlated with the differentiation degree of hepatocellular carcinoma, tumor embolus, TNM stage and the two-year survival rate after operation (P<0.05). The expression of PHD2in hepatocellular carcinoma was significantly correlated with the degree of tumor differentiation, TNM stage, tumor size, tumor metastasis and recurrence after operation (P<0.05). The expression of PHD3in hepatocellular carcinoma was highly correlated with the degree of tumor differentiation, tumor embolus, and the two-year survival rate after operation (P<0.05). (3) The expression of HIF-la in hepatocellular carcinoma was positive relative with the expression of PHD2(r=0.219, P=0.026). The expression of PHD1in hepatocellular carcinoma was positive relative with the expression of PHD3(r=0.201, P=0.042).(4) Survival analysis showed that the patients with positive expression of HIF-la, PHD1and PHD3had shorter survival time than those with negative expression. COX multivariate analysis showed that expression of PHD1was an independent prognostic factor for HCC patients.Conclusions:(1) The abnormal expressions of HIF-1α, PHD1, PHD2and PHD3were involved in the malignant pathological characteristics of hepatocellular carcinoma, which might be one of the important mechanisms of the carcinogenesis, tumor progression and aggressiveness in hepatocellular carcinoma.(2) Joint detection of HIF-1α, PHD1, PHD2and PHD3may be helpful to judge the degree of malignancy, potential metastasis and analyze the prognosis of hepatocellular carcinoma. |
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