The Significance Of Golgi Protein73Expression In Primary Hepatic Carcinoma

ObjectivesPrimary hepatic carcinoma(PHC) is one of the most common malignant tumor withhigh death rate in the world at present. Recently, Golgi protein73(GP73)，a resident golgiglycoprotein，was found to be up-regulated in sera of patients with liver disease, especiallyin that with PHC. So it is assumed that GP73might serve as a novel serum marker forearly PHC．The expression level of GP73was analyzed in the PHC tumor, tumor-adjacenttissue, cirrhosis liver tissue and normal liver tissue specimens. To explore the clinicalsignificance of GP73in PHC, serum GP73was analyzed in different types of PHC.Futhermore, GP73was analyzed to detect the value of diagnosis, monitoring of recurrence,prediction of metabasis and prognosis in PHC and to validate that combined detection ofGP73and other serum markers is helpful for diagnosis of PHC.Methods1、GP73were detected in26cases of primary hepatic carcinoma tissue,23cases of tumor-adjacent tissue,5cases of cirrhosis liver tissue and6cases of normal liver tissue by two step method immunohistochemical(IHC) method.2、Enzyme-linked immunosorbent assay(ELISA) were used to detect the serum GP73.We compared53cases of PHC experimental group,2control groups of liver diseases(including30cases of HBV-related hepatic cirrhosis,38cases of chronic hepatitis B,20cases of chronic hepatitis C) and other malignant tumor diseases(including15casesof secondary hepatocellular carcinoma,4cases of cholangiocarcinoma,4cases of lungcancer,10cases of breast cancer,5cases of rectal cancer,5cases of colon cancer,3cases of pancreatic cancer),8cases of recurrence monitoring group of PHC,13casesof evaluation group of therapeutic efficacy and20healthy persons. Serum AFP, CEA,CA199was also measured by chemiluminescence immunoassay analyzer and serumGGT, ALT, DBIL, TBA was measured by biochemical analyzer.Results1、The expression of GP73in primary hepatic carcinoma tissue and tumor-adjacent livertissue were postive, and the positive rate of GP73was significantly higher than that incirrhosis liver tissue and normal liver tissue (P <0.05).2、The serum GP73level in the PHC experimental group(306.43±101.52ng/ml) wassignificantly higher than the serum GP73level in HBV-related hepaticcirrhosis(140.68±52.52ng/ml), chronic hepatitis B(82.28±31.12ng/ml), liver diseasecontrol group, other malignant tumor disease control group and healthy controlgroup(48.08±32.94ng/ml)(P<0.05).3、The patients of PHC whose serum GP73is positive constitute75percent of the24casesof PHC whose serum AFP level is less than the critical value of400ng/ml. GP73hada better sensitivity compared to AFP(P<0.01).4、With the diagnostic criteria of GP73≥150ng/ml and AFP≥400ng/ml, ROC curveanalysis showed that, GP73had a better sensitivity(86.8％) compared to that ofAFP(54.7％)(P<0.01) while the specificity of GP73is lower than that of AFP (P<0.01).The area under the curve (AUC) of GP73and AFP for the diagnosis of PHC had no significant difference (GP73with0.886，AFP with0.932)(P>0.05).5、Further study found that, the serum levels of GP73and ALT, DBIL, TBA wereseparately highly correlated (Spearman correlation analysis, P<0.05).6、With the Spearman correlation analysis of influence factors of GP73level (includingpathological type, age, gender, tumor size, TNM stage, hepatic cirrhosis, intrahepaticand extrahepatic metastasis, portal vein tumor thrombus, ascites, hepatic hilar lymphnode metastasis), the analysis results showed that GP73level is related to theoccurrence of portal vein tumor thrombus (P<0.05).7、Among13cases of evaluation group of therapeutic efficacy with interventional therapyor operation resection of the tumor, there were three patients whose serum GP73leveldecreased after treatment. GP73level increased significantly in8cases of recurrencemonitoring group of PHC (P <0.05).8、Diagnostic sensitivity(98.1%) was obviously increased by the use of the combination ofGP73、APF、CEA、CA199and GGT.Conclusions1、GP73is highly expressed in the primary hepatic carcinoma tissue and can be used as anovel biomarker for PHC．2、Serum GP73can be used as a sensitive biochemical marker to reflect the liver injury ofPHC and has important clinical significance in the diagnosis of PHC, therapeuticefficacy observation, prognosis estimation and recurrence monitoring.3、Combination of serum GP73、APF、CEA、CA199and GGT is highly significant for thediagnosis of PHC and can be used as early PHC screening.