| Objective:Primary hepatic cancer(PHC) is a malignant tumor with poor prognosis. Although AFP is an index which used commonly, there are still a lot of PHC patients with AFP negative. Being lack of an ideal index which express in the early stage of (PHC) in serum and effective treatment to most patients diagnosed in mid or even late stage, the prognosis of these patients is poor.Because the cancer is easy to relapse and transfer,patients with PHC in late stage can not bear surgery even though cutted reluctantly it.So it is important to discovery PHC earlier to improve survival rates and life quality. The subject focused on GPC3 is to analyze AFP, GPC3, AFU and CA199 in the serum separately and combined detection for PHC to find better serum indexes for early diagnosis of PHC.Methods:1. Object:55 hospitalized patients with primary hepatic cancer diagnosed by surgery and pathology were selected in oncological surgery and digestive system department of Chengde Central Hospital from August 2009 to July 2011, including 32 males and 23 females,and the age was (54.4±11.9) years old. Select 30 cases of patients with cirrhosis in the same period, including 18 males and 12 females,and the mean age was (52.8±9.7) years old.The diagnostic criteria of cirrhosis is as follows:(1)There is a clear history of chronic liver disease or signs,(2)There was portal vein hypertension performance,(3)It shows cirrhosis through B-ultrasound or CT.The clinical data of HCC and cirrhosis patients were complete.30 cases of healthy persons in our hospital medical center in the same period are as control group, including 17 males and 13 females,and the mean age was (50.9±11.5) years old.The general information such as age,sex,ALT,AST,HBeAg and HCV antibody was balanced as consonance among the three groups(P>0.05).2. Specimen collection:2mL peripheral blood with no hemolysis or lipemia was collected in all of the subjects when they were fasting, the serum was separated and stored at -20℃ after centrifugating at 2000 r/min for 8 mm.3. Detection:Assay AFP,CA199 by chemiluminescence immune reagent in electrochemiluminescence immunoassay analyzer E601, AFU by velocity method, GPC3 by enzyme-linkedimmunosorbent assay(ELISA).Follow the instructions strictly according to the description when working.4. To determine cut-off values:Draw receiver operator characteristic curve(ROC) through SPSS 17.0 to determine the cut-off values of GPC3 and AFU by the maximum area under the curve.5. Statistical analysis:The statistical analysis was under SPSS17.0 statistical software, detection datas were expressed by x±s, comparisons of mean analysis of variance, comparisons of enumeration datas and rate chi-square test. The efficacy of the indexes above separately and joint diagnosis of PHC was evaluated by sensitivity [a/(a+c)], specificity [(d/(b+d)], diagnostic odds ratio (axd/bxc) and accuracy (a+d)/(a+b+c+d)]. (a is true positive cases; b is the number of false-positive cases; c is the number of false-negative cases; d is the number of cases of the true negative cases.)The joint detection criteria was as follows:As long as there is only one index more than the critical value in the combination,then judge it to be positive.If all the values are below the threshold, then judge it to be negative. There is statistically difference if P<0.05.Results:1. The tested results of indexes in PHC, liver cirrhosis and normal control group:GPC3 level in PHC, cirrhosis and control group was respectively 3.9±2.8ng/mL,0.6±0.5ng/mL,0.5±0.4ng/mL. Obviously compared with cirrhosis and control group,GPC3 in PHC group was significantly higer(P<0.05),GPC3 in cirrhosis group was significantly higher than that in control group (P<0.05); AFP in PHC,cirrhotic and normal group was respectively 242.3±12.5μg/L,143.2±10.6μg/L,11.2±3.4 μg/L, obviously AFP in PHC group was significantly higher than the other two groups(P<0.05), and AFP in cirrhotic group was significantly higher than that in normal group(P<0.05); AFU in PHC,cirrhotic and normal group was respectively:73.0±12.5U/L,12.1±4.8U/L/7.1±3.2U/L,obviously AFU in cirrhotic group was significantly higher than that in normal group (P<0.05), and there is no statistically difference in AFU between cirrhosis and control group(P>0.05).CA199 in PHC,cirrhotic and normal group was respectively 88.3±15.4U/ml,61.6±12.2U/ml,25.1±10.6U/ml,obviously CA199 in PHC group was significantly higher than the other two groups(P<0.05), and there is no statistically difference in CA199 between cirrhosis and control group(P>0.05).2. The cut-off value of GPC3 and AFU:When it is positive if GPC3>2 ng/mL,the maximum area under ROC curve of GPC3 was 0.755(95%CI: 0.578-0.786);When it is positive if AFU>35 U/L,the maximum area under ROC curve of AFU was 0.715(95%CI:0.599-0.830).3. The index separately tested in PHC group:The sensitivity, specificity and accuracy of AFP were as follows:74.5%,83.3%,77.6%; Of GPC3 were 78.2%,80.0%,81.2%;Of AFU were 70.9%,76.7%,72.9%;Of CA199 were 69.1%,76.7%,71.8%.4. The combined measurement of the indexes to diagnose PHC:The sensitivity, specificity and accuracy of GPC3 combined with AFP to diagnose PHC were respectively 92.7%,76.7% and 85.9%; The sensitivity, specificity and accuracy of AFU combined with AFP to diagnose PHC were respectively 80.0%,73.3% and 77.6%;The sensitivity, specificity and accuracy of CA199 combined with AFP to diagnose PHC were respectively 85.4%,70.0% and 80.0%; The sensitivity, specificity and accuracy of combined measurement of GPC3,AFP and AFU to diagnose PHC were respectively 94.5%,63.3% and 83.5%; The sensitivity, specificity and accuracy of combined measurement of GPC3,AFP and CA199 to diagnose PHC were respectively 96.4%,63.3% and 84.7%; The sensitivity, specificity and accuracy of combined measurement of AFP,AFU and CA199 to diagnose PHC were respectively 90.9%,60.0% and 80.0%; The sensitivity, specificity and accuracy of combined measurement of AFP,GPC3,AFU and CA199 to diagnose PHC were respectively 100%,40% and 78.8%.In two-two combined test,the sensitivity of AFP combined with GPC3 were highest(P<0.05),but there was no significant difference in specificity and accuracy(P> 0.05).The sensitivity of combined test of three indexes was higher than alone and two,but the specificity and accuracy was significantly lower;The sensitivity of combined test of four indexes was 100%,but the specificity was only 40%.The sensitivity and accuracy of AFP combined with GPC3 were significantly higher than that used only one index(P<0.05),but there was no significant difference in specificity(P>0.05).Conclusion:1. GPC3 can be used as a tumor marker which is of high expression in patients with PHC but low in patients with cirrhosis and healthy adult.2. AFP is a specific tumor marker which commonly used,and yet there is no better tumor markers utill now.The diagnosis of combination in GPC3,AFU and CA199 can improve the sensitivity, in which the sensitivity and accuracy of combination between AFP and GPC3 is best. In spite of the sensitivity of combined measurement of three indexes or four improved signifantly, the specificity decreased signifantly.3. The detection rate of GPC3 in AFP-negative patients with primary hepatic cancer was high, so the combining detection between GPC3 and AFP can improve the detection rate of primary hepatic cancer and improve the diagnosis of primary hepatic cancer earlier. |
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