| Primary hepatocellular carcinoma (PHC), which was known as the "King of cancer", is one of the most prevalent tumors worldwide. It has a high degree of malignancy, and the prognosis is extremely poor. China is a region with high incidence of PHC in the world. The mortality of PHC now ranks China tumor mortality of the two and has been on a steady upward trend in the past 10 years. Diagnosis of PHC has very important significance to the early detection and early treatment of PHC as well as to prolonging survival in patients with PHC. As the only one of the most widely used PHC tumor markers, alpha-fetoprotein (AFP) plays an important role in PHC diagnosis, differential diagnosis, prognosis and monitoring. But the AFP has a certain rate of misdiagnosis and missed diagnosis in the diagnosis of PHC, and the sensitivity of AFP is lower for small PHC. However, other indicators current applicated can't replace AFP as liver cancer tumor markers. In view of this, it is necessary to search for complementary new tumor markers and establish the most effective multi-target detection system to meet the clinical needs. In recent years, glypican-3(GPC3), as a tumor marker of liver cancer, was concerned by many scholars. Hsu first reported GPC3 mRNA expression increased in hepatocellular carcinoma, and found GPC3 mRNA in a higher expression in small hepatocellular carcinoma and AFP negative liver cancer in 1997. Capurro and others detected the GPC3 protein in the serum of patients with hepatocellular carcinoma and the positive rate in AFP negative liver cancer was 55% in 2003. All these give us to see the broad prospects of GPC3 as a novel tumor marker of liver cancer.Percutaneous radiofrequency ablation treatment (RFA) is a main non-vascular interventional treatment method of liver cancer. At present, monitoring the therapeutic effects of the intervention still use imaging examination and AFP detection. However, the imaging examination can not reflect necrosis of the tumor tissue, and factors such as the high cost of inspection, contact-ray, could not quantify et al. restricted their application in clinical practice; AFP detection, which is convenient and easy to repeat, can be quantified, is applied in clinical practice widely, but for AFP negative patients, there still lack of effective monitoring indicators of hematology.Objective: To determine the clinical values of serum GPC3 protein detection used singly or combined with AFP and CA199 in the diagnosis and differential diagnosis of liver cancer, and further to explore its values in monitoring the therapeutic effects of RFA in the treatment of liver cancer. Method: Choose 38 cases of liver cancer patients as liver cancer group, patients were clinically diagnosed with PHC according to the guidelines for PHC diagnosing established by chinese anti-cancer association in 2001, Guangzhou and/or had pathology diagnosis, and clinical history data integrity, 29 cases of men and 9 cases of women aged 35 to 83 years old. 17 cases of them received radiofrequency ablation treatment as a treatment group, 12 cases of men and 5 cases of women aged 41 to 83 years old. Choose 14 cases of liver hepatitis or cirrhosis patients as hepatitis and cirrhosis group, 10 cases of men and 4 cases of women aged 21 to 85 years old. Choose healthy donors 10 cases as a normal control group, 6 cases of men and 4 cases of women aged 24 to 76 years old.Collected the serum samples of patients in different groups, encoded and preservated into -75℃refrigerator. Serum GPC3 protein detected using ELISA kits. AFP, CA199 detected by radioimmunoassay method.Using SPSS14.0 software for statistical analysis. Applying nonparametric tests of 2 independent sample test, 2 related sample test,χ2 test, Fisher exact probability method, spearman rank correlation analysis. Inspection standards P<0.05 to have statistical difference, P<0.01 to have significant statistical difference.Results: 1 Serum GPC3 protein level in 10 healthy blood donors was 159.97(129.27,172.35) ng/ml, and in hepatitis or cirrhosis patients was 271.92(154.64,301.81) ng/ml, PHC patients 337.00(181.67,564.83) ng/ml.2 The serum GPC3 protein level of PHC was significantly higher than normal level of the control group (U=70.000, P <0.01), the serum GPC3 protein level of hepatitis and cirrhosis group was higher than normal level of the control group (U=31.000, P<0.05), the serum GPC3 protein level of PHC was higher than the level of hepatitis and cirrhosis group, but no statistical significance was observed (U=204.000, P>0.05).3 In radiofrequency ablation treated group, the serum GPC3 protein level before treatment was 425.40(253.73,681.20) ng/ml, 7 days after treatment was 375.66(178.87,632.66) ng/ml, 14 days after treatment was 287.77(144.78,420.87) ng/ml. 7 days after treatment, the serum GPC3 protein level was lower, but no statistical significance was observed (Z=-0.402, P>0.05). 14 days after treatment, the serum GPC3 protein level was the lowest, and significant difference could be observed (Z=-2.485, P<0.05).4 Results from the GPC3-ROC curve analysis (A=0.700, P<0.01) showed that the best diagnostic threahold was 387.59 ng/ml. When the cutoff point was at 387.59 ng/ml, its sensitivity was 47.4% and its specificity was 95.8%, the Youden's index was 0.432.5 The relationships between the serum GPC3 protein and the clinical parameters5.1 The positive rate of serum GPC3 protein in large liver cancer (≥5 cm) was 47.62% (10/21), in small liver cancer (<5 cm) was 72.73% (8/11), showed no statistical difference (P>0.05).5.2 The positive rate of serum GPC3 protein in liver cancer with metastasis was 75.00%(6/8); in liver cancer absence of metastasis was 52.00%(13/25), showed no statistical difference (P>0.05). The positive rate of serum GPC3 protein in liver cancer with portal vein thrombosis was 66.67%(6/9); in liver cancer without portal vein thrombosis was 54.18%(13/24), showed no statistical difference (P>0.05). The positive rate of serum GPC3 protein in liver cancer with multiple nodules was 75.00%(9/12); in liver cancer with single nodules was 45.00%(9/20), showed no statistical difference (P>0.05).5.3 The positive rate of serum GPC3 protein in liver cancer with liver function (TBIL, ALB) abnormalities was 58.82%(10/17), in liver cancer with normal liver function (TBIL, ALB) was 54.54%(6/11), showed no statistical difference (P>0.05). The positive rate of serum GPC3 protein in liver cancer with liver injury (AST, ALT abnormal) was 69.23%(9/13); in liver cancer with normal AST and ALT was 46.67%(7/15), showed no statistical difference (P>0.05).5.4 The positive rate of serum GPC3 protein in liver cancer had recurrence after treatment was 66.67%(8/12), in liver cancer did not recurrent after treatment was 52.38%(11/21), showed no statistical difference (P>0.05).6 The serum GPC3 protein and AFP levels had no significant correlation (r=0.205, P=0.141>0.05); the serum GPC3 protein and CA199 levels had no significant correlation (r=-0.021, P=0.886>0.05); there was no obvious correlation between the serum CA199 and AFP levels (r=-0.017, P=0.910>0.05). In liver cancer group, of serum GPC3 protein, the positive rate was 47.37%; AFP, the positive rate was 54.84%; CA199, the positive rate was 42.11%. Serum GPC3 protein and AFP in PHC combined detection rate was 80.65%; serum CA199 and the AFP jointed detection rate was 65.79%; combined of the three, the detection rate was 85.71%.7 The positive rate of serum GPC3 protein in AFP negative liver cancer was 57.14% (8/14), in the AFP positive liver cancer, the positive rate was 52.94% (9/17), showed no statistical difference (P=1.000>0.05). The positive rate of serum GPC3 protein in small liver cancer was 72.73% (8/11); the positive rate of AFP in small liver cancer was 27.27% (3/11). Combined serum GPC3 protein and AFP, the positive rate was 81.82% (9/11).Conclusions: 1. The serum GPC3 protein level in PHC, hepatitis and liver cirrhosis were all significantly higher than that of healthy people. From the highest to the lowest they were PHC, hepatitis and liver cirrhosis and healthy people.2. The serum GPC3 protein levels of patients with liver cancer decreased after radiofrequency ablation treatmented, could be used as indicator for monitoring the therapeutic effects and recurrence.3. The sensitivity and specificity of serum GPC3 protein in liver cancer diagnosis were 47.4% and 95.8%. It might have a certain value in the diagnosis of PHC.4. There showed no statistical significant correlations between the serum GPC3 protein and liver cancer clinical parameters such as tumor sizes, the presence of extrahepatic metastasis, portal vein thrombosis, the recurrence after treatment, abnormal liver function, liver damage and the number of liver cancer nodules.5. There had no significant correlation between serum GPC3 protein and AFP, CA199 levels. Jointed the three detection could improve the sensitivity for diagnosing PHC.6. Serum GPC3 protein had a higher positive rate in AFP negative liver cancer and small liver cancer, could be a complementary tumer marker for AFP.
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