Action And Significance Of TACE On Serum Levels Of CTGF And VEGF In HCC Patients.

Backgrounds and PurposesTranscatheter arterial chemoembolization (TACE) exploits the arterial hypervascularization of HCC that receives blood from newly fromed arteries, whose occlusion and embolization with an emulsion of chemotherapeutic drug and lipiodol induce tumor necrosis. TACE is recommended as fist line non-curative therapy for non-surgical patients with HCC. Inducing ischemic tumor necrosis by acute arterial obstruction, TACE creates the hypoxic tumor microenvironment which could hypothetically provoke a neoangiogenic reaction and the change of invasive ability of the tumor that potentially interfer with its effectiveness. Vescular endothelial growth factor (VEGF) promotes angiogenesis and overexpression of VEGF is related to maliganacy of tumor. Connective Tissue Growth Factor (CTGF) as a matricellular protein is a member of the CCN protein family. These proteins have been implicated in various biological processes, including cell proliferation, adhesion and angiogenesis. Recent studies show that CTGF can promote the growth of HCC xenograft in nude mice and tumor cell intravasation. Hypoxic condition can induce the expression of Hypoxia inducible factor-1α(Hif-1α) which can regulate the transcription of VEGF and CTGF. No reports concerning the action of the hypoxic tumor microenvironment that TACE creates on the serum level of CTGF in HCC patients has been found. In this study, we evaluated serum levels of Hif-1α、VEGF and CTGF in HCC patients who had received TACE treatment before, who had never received TACE or before and after TACE to investigate the effect of TACE on the invasiveness of HCC cell.Methods 1. The blood samples were provided from67HCC patients treated at Shandong Provincial Hospital between September2011and January2012, in which35patients had received one to three courses of TACE, the other32patients had received no treatment of any kind;28of the67HCC patients undergoes TACE, sera samples were collected from each patient before TACE, and1day after TACE.2. Hif-1α、VEGF and CTGF were measured by ELISA in sera of all patients.3.Statistical analysis Mann-Whitney U test and person analysis.ResultsSera concentration of VEGF and CTGF correlated significantly with two clinicopathological parameters, big tumor size and portal vein invasion; Sera levels of VEGF�'�CTGF of TACE group were significantly hgher than that of non-TACE group (P<0.05); No significant difference had been found in sera level of VEGF and CTGF between before TACE and1day after TACE in the28HCC patients; sera Hif-1α level correlated positively with sera VEGF level (r=0.858, P<0.001); sera Hif-1α level correlated positively with sera CTGF level (r=0.852, P<0.001) and sera VEGF level correlated positively with sera CTGF level (r=0.963, P<0.001)Conclusions1. Sera concentration of VEGF and CTGF correlated significantly with two clinicopathological parameters, big tumor size and portal vein invasion, it indicated that serum levels of VEGF and CTGF may related to the invasiveness and growth of HCC;2. Sera levels of VEGF�'�CTGF of patients who had received TACE before were significantly hgher than that of patients who had’t, it indicated that TACE may promote expression of VEGF and CTGF, which might be the mechanism of reccurence and metastasis of tumor after TACE.3. Sera Hif-1α level correlated positively with serum VEGF level; serum Hif-1α level correlated positively with serum CTGF level, it indicated that the hypoxic tumor microenvironment TACE create could induce the expression of Hif-1α which might result in increased expression of VEGF and CTGF.