| BackgroundPrimary liver cancer (PLC) is one of the most common cancers in the world and the second most frequent cause of mortality amongst oncological patients. Possibly most striking of all, over half of new cases and deaths occur in China, and the incidence of PLC is still on the increase. The diagnosis of PLC is usually made at an advanced stage owing to hiding on setting and lack of clinic features, which limits the application of radical surgery. Therefore, the key to performing earlier treatment and lowering death rate are the early finding, early diagnosis and early treatment.At the present time, the diagnostic method of PLC recommended by clinical practice is alpha-fetal protein (AFP) detection. This approach, too, has its limitations:about 30% to 40% of PLC patients show negative or low level of AFP. Some patients can have an elevated AFP without the presence of PLC, such as acute viral hepatitis, chronic active hepatitis, cirrhosis active stage and some other diseases like carcinoma of testis or ovarian cancer. Therefore, finding out a serum marker of PLC with higher sensitivity and specificity is one of hot spots in medical science.Golgi protein-73 (GP73) is newly-discovered tumor marker, recent reports suggest that GP73 is a possible marker for PLC with better sensitivity and specificity than AFP. Guangxi has particularly high PLC rates, and the annual death rate of PLC is 34.39 per 100,000, which account for 34.12% of total mortality of malignant tumor. PLC now is the leading cause of cancer death in Guangxi province. Therefore, the research of GP73 in the diagnosis of PLC carried out in Guangxi is regional representative and unique, and would provide reference for clinical application. In virtue of the clue, we take the patients with PLC in Guangxi as the research object and assess the effect of GP73 on the diagnosis of PLC.MethodsThe expression of GP73 in PLC tissue1. The immunohistochemical SP staining technique was used to detect the expression of GP73 and AFP in 92 cases of PLC, adjacent tissue and 29 normal controls. The correlation between the expression of GP73 and clinical pathology parameters of PLC was analyzed.2. Western blotting was also used to examine the expression of GP73 in 92 cases of PLC, adjacent tissue and 29 normal controls. The correlation between the test results of immunohistochemical SP staining technique and western blotting was analyzed.Serum GP73 levels in patients with PLCThe peripheral serum samples from 1201 individuals were collected, including 403 PLC patients,162 cirrhotic patients,200 hepatitis B patients,107 hepatitis B virus carriers,29 patients with benign liver tumor,140 patients with other malignancies, and 150 healthy volunteers (as the controls). The expression levels of serum GP73 and alpha-fetal protein (AFP) were detected by double antibody sandwich ELISA and electrochemiluminescence assay.Dynamic monitoring of serum GP73 levels of in PLC patients with hepatectomy and PLC high-risk group1. The dynamical serum GP73 levels were studied in 79 patients with PLC before and after hepatectomy. The expression levels of serum GP73 and alpha-fetal protein (AFP) were detected by double antibody sandwich ELISA and electrochemiluminescence assay.2. Follow-up was carried out routinely to PLC high-risk group involving 132 patients. Serum GP73 levels were tested at the check-up by double antibody sandwich ELISA.ResultsThe expression of GP73 in PLC tissue1. The results of immunohistochemical SP staining technique①An increase of expression of GP73 in PLC and adjacent tissue was detected by immunohistochemical SP staining technique, the positive rate of GP73 was higher than that of AFP in PLC and adjacent tissue (97.8%vs.71.7%,92.3% vs. 54.3%, P<0.05). The test results of GP73 and AFP in normal control were all negative.②The expression of GP73 was positively correlated with pathologic grade and Child-Pugh grade(P<0.05), but not correlated with age, gender, AFP, tumor size, cirrhosis, HBV, lymph node status, portal vein tumor thrombus and clinical stage.2. The results of Western Blotting①The gray-scale value of GP73 in PLC tissue, adjacent tissue and normal tissue were 6.28±23.22,1.58±7.58 and 1.58±7.58, respectively. The gray-scale value of GP73 in PLC tissue was higher than those in the other groups, and those in adjacent tissue were higher than that in normal control (both P<0.05).②The positively correlated between the results tested by Western Blotting and immunohistochemical SP staining technique was been shown, P<0.05.Serum GP73 levels in patients with PLC1. The expression levels of serum GP73 from the PLC patients were significantly higher than those from cirrhotic patients, hepatitis B patients, hepatitis B virus carriers, patients with benign liver tumor, patients with other malignancies and healthy volunteers (324.38±56560.00 vs.93.12±4072.77, 23.48±146.82,16.63±137.73,6.84±37.57,7.22±88.49,12.68±79.36, P<0.05).2. The cut off value of GP73 and AFP were determined as 65.25 ng/mL and 39.32 ng/mL by the receiver operating characteristic (ROC) curve, respectively, when the sensitivity and specificity of GP73 for the diagnosis of PLC were both higher than those of AFP (82.3% vs.72.2%; 82.7% vs.79.4%; both P<0.05). The area under curve of GP73 and AFP were 0.865和0.792(P<0.05), respectively.3. GP73 levels were elevated in the serum of 84.0%(94/112) of individuals with PLC who had serum AFP levels less than≤39.32 ng/mL4. The sensitivity and specificity of GP73 in combination with serum AFP for the diagnosis of PLC were 94.4% and 73.2%, the negative predictive value and Youden's index improved to 0.970 and 0.676, respectively.5. For 75 cases of small liver caner in PLC group, there were 49 cases of GP73> 65.25 ng/mL and 35 cases of AFP>39.32 ng/mL, GP73 levels had significantly higher detection rate than AFP for diagnosing small liver caner, P<0.05.6. There was no correlation between serum GP73 and AFP levels in each group.Dynamic monitoring of serum GP73 levels of in PLC patients with hepatectomy and PLC high-risk group1.79 patients were followed up at 8 months after hepatectomy, median follow-up was 8 months, and final follow-up ratio was 84.8%. GP73 levels of GP73-positive PLC patients dropped dramatically in 1 to 8 weeks after hepatectomy. GP73 levels of GP73-negtive PLC patients did not drop significantly. However, GP73 levels were elevated in the serum of 5 cases of GP73-negtive PLC patients in 1 week after hepatectomy, and then fell to normal level in 2 to 8 weeks.2. During follow-up of 8 months, there were 3 cases of recurrent PLC patient, which serum GP73 levels after recurrence were higher than pre-recurrence, but the difference was not significantly(P=0.111).There was 1 case of AFP-negative PLC patient, which levels of serum AFP did not rise during follow-up. On the contrary, GP73 level was elevated before the operation, and remained in high after hepatectomy. The level of serum GP73 was higher than the one before at 24 weeks after hepatectomy(16 weeks-47.3 ng/mL,24weeks-57.29 ng/mL), and rise further when the patient relapsed at 28 weeks(139.66 ng/mL).3. The PLC high-risk group was followed up at 6 months, median follow-up was 6 months, and final follow-up ratio was 72.0%. Re-check was performed once, and new liver cancer case was not been found. The difference between serum GP73 levels before and after re-check was significantly (20.13±323.86 vs.23.17±297.30, P=0.000).Conclusions1. GP73 highly expresses in PLC and adjacent tissue, the positive rate of GP73 is higher than that of AFP in PLC and adjacent tissue. GP73 expression is positively correlated with pathologic grade and Child-Pugh grade.2. GP73 is a new serum marker for the diagnosis of PLC, with higher sensitivity and specificity than AFP, and improves the detection rate of PLC patients with AFP-negative. The diagnostic rate of GP73 for small liver cancer is higher than AFP.3. The rate of missed diagnosis for PLC patient with AFP-negative or low can be reduced by combined examination of serum GP73 and AFP, at the same time, the detection rate and accuracy for the diagnosis of PLC is improved, too. GP73 is recommended for clinical application, as an effective serum marker for the detection of PLC.4. Dynamic monitoring of serum GP73 levels has certain value in evaluation of therapeutically effect, judgment of pre-alarm PLC. ObjectiveTo observe the diagnostic value of golgiprotein-73 (GP73) in patients with primary liver cancer by a Meta-analysis.MethodsSuch databases as PubMed, EMbase, PML, Springer Link, Ebsco, CMB,VIP Information, WanFang Data and CNKI (from the date of their establishments to February 2012) were searched. Qualified studies of GP73 in diagnosis of liver cancer in english and chinese published were collected. Two reviewers independently assessed the methodological quality of each study with the tool of quality assessment of diagnostic accuracy studies (QUADAS), and extracted the characteristics of the included articles. Statistical analyses were performed by software Meta-Disc 1.4 vision. The pool sensitivity, specificity and diagnostic odds ratios (DOR) were calculated, and summary receive operating characteristic (SROC) curve was performed.ResultsEighteen of retrieved articles were included. The included studies had heterogeneity. The pool sensitivity and specificity for GP73 and 95% confidence interval (95%CI) was 0.76[95%CI(0.75,078)]and 0.87[95%CI(0.86, 0.88)], respectively. The pool DOR was 16.71 [95%CI(8.54,32.74)], the AUC of SROC was 0.858. Sensitivity analysis demonstrated no disproportionate influences of individual studies. Begg funnel plot suggested the publication bias was not significant (Begg's test P= 0.130, Egger's test P= 0.192).ConclusionsMeta-analysis indicates that GP73is a valuable diagnostic method which has higher sensitivity and specificity in detecting liver cancer. However, more supports from high quality prospective researches are desired.
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