Changes And Significance Of Serum VEGF、CTGF、HIF-1α And OPN Before And After TACE In Primary Hepatocellular Carcinoma Patients

Objective:The study was focused on the dynamic changes of serum VEGF (Vascular endothelial growth factor)、CTGF(Connective tissue growth factor)、HIF-1α (Hypoxia inducible factor-1α)and OPN (Osteopontin)before and after TACE(Transhepatic artery chemoembolization) in primary hepatocellular carcinoma (HCC)patients, to explore the relationship between clinic and imaging features and the four factors. Then,we can analysis the effect of TACE on invasion and metastasis of HCC.Methods:We chose31patients with HCC treated in Shandong Provincial Hospital from June2012to February2013. Serum samples were collected from each patient before TACE,1day,3days,5days and7days after TACE.15cases of healthy persons as a healthy control group. The dynamic changes of serum VEGF、CTGF、HIF-1α and OPN were measured by ELISA. Then analysis the link between VEGF, CTGF, HIF-1α and OPN preoperative levels and fluctuation ranges with clinic and imaging features,such as tumor diameter, distant metastasis, portal vein invasion and HBsAg. T test and spearman correlational analyzation were carried out on the basis of SPSS17.0.Results:(1) Serum levels of VEGF, CTGF, HIF-1a and OPN in HCC patients before TACE were significantly higher than that in the control group (P<0.05); The concentration of VEGF and CTGF in1day,3days and5days after TACE were higher than preoperative (P<0.05), and VEGF concentration peak appeared at1day after TACE, while CTGF appeared at3days after TACE, both showed no significant differences between7days after TACE and the preoperative (P>0.05); The concentration of HIF-1a and OPN after1day,3days,5days,7days were higher than the preoperative (P<0.05), and both concentration peak appeared at1day after TACE; The concentration of VEGF, CTGF, HIF-1a and OPN after7days were significantly lower than lday after TACE(P<0.05).(2) VEGF, CTGF, HIF-1α and OPN preoperative levels and fluctuation ranges were significantly correlated with the presence of distant metastasis before TACE(P<0.05), VEGF preoperative level was significantly correlated with greater tumor diameter (P<0.05), the fluctuation ranges of CTGF and OPN were significantly correlated with portal vein invasion and positive HBsAg (P<0.05).(3) In the serum of HCC patients, HIF-1a and VEGF levels were positively correlated (r=0.870, P<0.001), HIF-1α and OPN levels were positively correlated (r=0.807, P<0.001), OPN and VEGF levels were positively correlated (r=0.712, P<0.001).Conclusion:(1) Serum levels of VEGF, CTGF, HIF-1a and OPN in HCC patients before TACE were significantly higher than that in the control group, suggesting that they played a role in the occurrence and development of liver cancer. VEGF, CTGF, HIF-1α and OPN in lday,3days,5days after TACE were higher than the preoperative, and VEGF, HIF-1α and OPN peak period appeared one day after TACE,while CTGF appeared3days after TACE, which related to hypoxic microenvironment caused by TACE. The concentration of VEGF, CTGF, HIF-1α and OPN after7days were significantly lower than lday after TACE, especially VEGF and CTGF after7days showed no significant difference with the preoperative.(2) VEGF, CTGF, HIF-1a and OPN preoperative levels were significantly correlated with distant metastasis, VEGF preoperative level was significantly correlated with greater tumor diameter, suggesting that the four factors were associated with the growth and invasion of tumor. The fluctuation ranges of the four factors were significantly correlated with distant metastasis, besides, the fluctuation ranges of CTGF and OPN were also significantly correlated with portal vein invasion and positive HBsAg.(3) In the serum of HCC patients, HIF-1a and VEGF, OPN were respectively positively correlated, suggesting that HIF-1α may promote tumor angiogenesis by upregulating VEGF and OPN level. VEGF and OPN levels were positively correlated, suggesting that OPN may promote tumor angiogenesis by upregulating VEGF level.