| Objectives:To investigate the characteristics of the whole-liver perfusion imaging by using a320-detector row CT in primary hepatocellular carcinoma (HCC), and their relationships with the microvessel density of HCC’s carcinoma tissues and the expression levels of related cytokines of Ang-2, Snail-2, Twist-1, E-cadherin and PAK4. To investigate the correlation between the characteristics of the whole-liver perfusion imaging by using320detector row CT and pathological grade in primary hepatocellular carcinoma, and explore its value in evaluating angiogenesis and pathological grade of HCC.Methods:By taking the prospective study methods,30primary hepatocellular carcinoma patients who conform to the accepting standard were chosen as the primary hepatocellular carcinoma group. Meanwhile,10normal volunteers were selected for the normal control group. All patients were scanned by320detector row CT of the whole-liver perfusion imaging.The images were post-processed by selecting the region of interest(ROI), generating time-density-curve (TDC) and color images of hepatic perfusion, and obtaining the perfusion parameters: hepatic arterial perfusion(HAP), hepatic portal perfusion (HPP) and hepatic perfusion index (HPI). The expression level of CD105, Ang-2, Snail-2, Twist-1, E-cadherin and PAK4were observed in specimens of both groups by Immunohistochemical staining, and pathological grade for the carcinoma tissues in the HCC group was judged according to Edmondson-Steiner grading system. The differences of CT perfusion parameters and the expression level of related cytokines between the HCC group and the normal control group were statistically analyzed. Pearson correlation analysis or Spearman rank correlation analysis was performed to determine the correlation among the four indexes respectively:CT perfusion parameters, microvessel density (MVD) which was marked with CD105, the expression of the cytokines which was related with the angiogenesis, and pathological grade of the carcinoma tissues in HCC group.Results:1. HAP, HPP and HPI in the hepatic tissues of the normal control group were respectively35.79ml/100ml/min,130.61ml/100ml/min, and22.63%, and those of the carcinoma tissues in HCC group were respectively85.54ml/100ml/min,75.34ml/100ml/min and58.03%. HAP and HPI in carcinoma tissues of the HCC group were significantly higher than those of the hepatic tissues in normal control group(P<0.01), and the HPP was significantly lower than that of the normal control group(P<0.01).2. In carcinoma tissues of the HCC group, CD105over-expressed. In the experiment, CD105was used to mark MVD. The difference of MVD between the HCC group and the normal control group was of statistical significance(P<0.01).3. In carcinoma tissues of the HCC group, HAP and HPI were positively correlated with MVD (r values were respectively0.600and0.648, P<0.01); HPP of the carcinoma tissues in HCC group was not correlated with MVD(r=-0.182, P=0.336).4. In carcinoma tissues of the HCC group, Ang-2, Snail-2, Twist-1and PAK4were over-expressed, and the differences between their expression and those of the normal control group were of statistical significance (P<0.01). In carcinoma tissues of the HCC group, the expression of E-cadherin was lowered, and the difference between its expression and that of the normal control group was of statistical significance (P<0.01).5. In carcinoma tissues of the HCC group, the expression of Ang-2, Snail-2, Twist-1and PAK4were positively correlated with MVD (r values were respectively0.697,0.764,0.641and0.597, P<0.01). The expression of E-cadherin of the carcinoma tissues in HCC group was not correlated with MVD(r=-0.199, P=0.291).6. In carcinoma tissues of the HCC group, the expression of Ang-2, Snail-2, Twist-1and PAK4were positively correlated with HAP (r values were respectively0.430,0.551,0.582and0.615, P<0.05); The expression of E-cadherin of the HCC group was not correlated with HAP and HPI (r values were respectively-0.301,-0.273, P values0.106,0.145). In carcinoma tissues of the HCC group, the differences of HPP in the expression of Ang-2, Snail-2, Twist-1and PAK4had no statistical significance (P>0.05).7. Pathological grade of HCC was positively correlated with carcinoma tissues’ MVD (r=0.896, P<0.01). In carcinoma tissues of the HCC group, the expression of Ang-2, Snail-2, Twist-1and PAK4were positively correlated with pathological grade (r values were respectively0.615,0.741,0.675and0.768, P<0.01), however the expression of E-cadherin was not correlated with pathological grade (r=-0.289, P=0.122). Pathological grade of HCC was positively correlated with HAP and HPI(r values were respectively0.873and0.868, P<0.01).8. In carcinoma tissues of the HCC group, the expression of Snail-2was positively correlated with Twist-1(r=0.660, P<0.01). In carcinoma tissues of the HCC group, the expression of Snail-2and Twist-1were not correlated with E-cadherin (r values were respectively-0.133and-0.193, P values were respectively0.484and0.306).Conclusions:1. Perfusion parameters obtained from the whole-liver perfusion imaging at320-detector row CT can quantitatively reflect the overall hemodynamical change of the lesions of HCC. To some degree, perfusion parameters of HAP and HPI of HCC can reflect the microvessel density and pathological grade of HCC, which can hopefully become a new way to evaluate noninvasively angiogenesis of HCC and tumor’s malignant degree in vivo.2. The fact that in carcinoma tissues of the HCC present over-expression of Ang-2, Snail-2, Twist-1and PAK4and that those expression levels were positively correlated with tumor microvessel density explains that they may take part in angiogenesis. The fact that expressions of Ang-2, Snail-2, Twist-1and PAK4in carcinoma tissues of HCC were correlated with tumor pathological grade and tumor CT perfusion parameters HAP and HPI explains that these cytokines are correlated with tumor’s biological behaviors like malignant degrees etc., which can be reflected to some degree through the change of tumor CT perfusion parameters. |
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