Expression And Significance Of Serum Protien Glypican-3, Survivin In Hepatocellular Carcinoma

Hepatocellular carcinoma(HCC) is the sixth most common malignant neoplasm and the third most common causes of cancer-related death worldwide. Thus, novel and promising makers are needed to be identified to improving the diagnostic accuracy of HCC. Survivin is the minimum inhibition of apoptosis protein which plays an important role in inhibiting apoptosis and regulating mitosis. Recent studies reported that survivin highly expressed in almost all human tumors and fetal tissue, but could be undetectable in normal human tissue, suggesting that survivin was associated with the occurrence and progress of carcinoma. However, only two studies reported the expression of survivin in serum of patients with HCC. Glypican-3(GPC3)belongs to the glypican family of glycosyl-phosphatidyl-inositol anchored heparan sulphate proteoglycans, which plays an important role in cellular growth, differentiation and migration. Several studies have reported that GPC3 was absent in normal human tissues but highly expressed in fetal liver, HCC tissues and most HCC cell lines. These studies indicate that GPC3 has been regarded as a useful histological maker in the diagnosis of HCC. Several subsequent studies have found that serum GPC3 had raised level in patients with HCC and lack of correlation with AFP. But it remains controversial about the diagnostic value of serum GPC3, especially when compared with AFP. In this study, we aimed to evaluate the clinical utility of survivin and GPC3 as a serum marker for HCC by ELISA.Aim:1.We evaluated the potential diagnostic value of serum survivin for hepatocellular carcinoma and found a ELISA kit performed better by detecting the concentration of serum survivin in patients with HCC by two kinds of ELISA kits. 2.We assessed the clinical utility of serum GPC3 for the diagnosis of HCC, especially compared with AFP.Methods: 1. The concentration of serum survivin was assessed in specimens of HCC, liver cirrhosis, Chronic hepatitis B and normal liver by ELISA with two kinds of ELISA kit(R&D and abnova). The correlation and difference between the two results were analyzed. 2.We recruited a total of 890 patients, including 283 cases with HCC, 267 cases with cirrhosis(LC), 162 cases with chronic hepatitis B(CHB), 16 cases withAH and 162 cases normal controls(NC) volunteers. The levels of GPC3 protein in serum were detected by ELISA by two independent researchers who had no access to clinical information of patients. In addition, serum AFP was also measured.Results: 1. The?positive?ratio?of?serum survivin detected by RD ELISA kit in all and HCC patients were 8.75%(7/80), 5%(1/20), respectively. For the same samples detected by abnova ELISA kit, the positive?ratio?of?serum survivin in all and HCC patients were 22.5%(18/80), 25%(5/20), respectively. The results measured by the two ELISA kits showed no significant difference between HCC patients and normal controls;( The correlation coefficient was 0.0064(P = 0.481) when detecting the same serum samples by two different ELISA kits and the?higher positive?ratio?of?serum survivin was observed in the patients detected by the abnova kit. Significant difference of the detection results was observed between RD kit and abnova kit. 2. The media level of serum GPC3 in patients with HCC, AH, LC, CHB and NC was 0 ng/ml(range=0-14.0ng/ml), 0 ng/ml(range=0-0ng/ml), 0ng/ml(range=0-12.5ng/ml), 0 ng/ml(range=0-1.7ng/ml), and 0ng/ml(range=0-4.3ng/ml), respectively. There was an elevation of serum GPC3 in patients with HCC(P=0.033) and LC(P=0.001) compared with those in NC, but no difference between HCC and LC(P=0.097). The AUC of ROC curve for HCC vs. all controls was 0.519, with a sensitivity of 39.9%, a specificity of 60.6%, and an optimal cut-off value of 0.002 ng/ml. No significant correlation was observed between serum GPC3 and AFP(P>0.05). We found 44 HCC patients had a elevation level of GPC3 in 121 patients who were negative for AFP.Conclusions: 1. The concentration of serum survivin was significantly lower than the lower limit of detection of two kinds of kits, which suggested both RD and abnova ELISA kits were not suitable for detecting serum survivin level in HCC patients. 2. There was no clinical utility of serum GPC3 for diagnosis of HCC, but it could be complementary to AFP to elevate the sensitivity of diagnosis for HCC.