| BackgroundDecoy receptor 3 (DcR3), a newly identified member of the tumor necrosis factor receptor (TNFR) super-family, act as a death decoy to prevent apoptosis mediated by TNFR family members such as Fas, LTβR and DR3. It is overexpressed in many various kinds of malignant tumors. Because it lacks an apparent transmembrane domain in its sequence, it is a secreted protein. Elevated serum DcR3 was detected in many kinds of tumor patients. Our previous data showed that DcR3 mRNA and protein were both over-expressed in hapatocellular carcinoma (HCC) tissues and HCC cell lines, and can accelerate the apoptosis of the tumour cells. In order to investigate the diagnostic and prognostic value of serum DcR3 in HCC, in this study we detected the serum DcR3 in HCC, analyzed the relation of serum DcR3 level and clinicopathological features, investigated the diagnosis value of HCC by combined detection of alpha fetoprotein (AFP) and DcR3.Materials and Methods1. All of 165 preoperative serums were collected from 67 patients with HCC, 34 patients with gastric carcinoma, 39 patients with breast carcinoma, 8 patients with liver cirrhosis, and 17 patients with cholecystitis. Twenty-eight normal individual serums were collected from healthy individuals as control group.2. ELISA was used to detect the serum DcR3 levels. The relation of serum DcR3 levels and clinicopathological features of HCC was analyzed.3. Chemiluminescence was used to detect the serum AFP levels. The results used to analyze the diagnosis value of HCC by combined detecting AFP and DcR3.4. Sixty-four paraffin blocks of HCC postoperative resection tissue corresponding with 67 HCC serums were collected. Immunohistochemistry was used to detect the expression of DcR3 in HCC tissues. The results used to analyze the correlation and the detection percentage of serum level and tissue expression.Results1. The levels of serum DcR3: The serum DcR3 levels and DcR3 positive incidence were 197.07±90.34pg/ml, 76.12% (51/67) in HCC; 194.87±98.38pg/ml, 73.53% (25/34) in gastric carcinoma; 130.64±51.76pg/ml, 41.03% (16/39) in breast carcinoma; 179.81±102.74pg/ml, 62.50% (5/8) in liver cirrhosis; 101.59±24.51pg/ml, 17.65% (3/17) in cholecystitis; 96.69±16.05pg/ml, 3.57% (1/28) in normal individuals, respectively. The levels of serum DcR3 in HCC, gastric carcinoma and breast carcinoma patients were significantly higher than that in the normal individuals(P<0.01), respectively. The serum DcR3 levels between HCC and gastric carcinoma patients had no difference(P>0.05), but they were significantly higher than that in breast carcinoma patients(P<0.01). The levels of serum DcR3 in HCC and liver cirrhosis patients were significantly higher than that in the normal individuals and cholecystitis patients (P<0.01), respectively. The serum DcR3 levels between HCC and liver cirrhosis patients, normal individuals and cholecystitis patients had no difference(P>0.05). 2. Serum DcR3 levels of HCC were significantly correlated with sex(P<0.01), cirrhosis(P<0.01), capsular infiltrate(P<0.05), recidivism or metastasis (P<0.05)and TNM staging(P<0.01). They were not associated with age, serum AFP levels, tumor node, tumor size, formation of tumor embolus, histological classification(P>0.05).3. The positive rate of AFP and DcR3 in HCC were 82.09% and 76.12%, respectively. But the positive rate was increased to 92.54% by the combined detection. The specificity and positive predictive value were decrease. However, negative predictive value, Youden's index and crude accuracy were increased.4. There was positive correlation between the serum level and tissue expression of DcR3 in HCC(rs=0.472, P<0.01). The positive rates of DcR3 in HCC tissue were 62.50% (40/64), which was significantly lower than that in serum (76.56%, 49/64) (P<0.05).ConclusionsThe levels of serum DcR3 in HCC patients were obvious higher than in healthy controls, and elevated serum DcR3 had significantly correlation with development, invasion and metastasis of HCC. Patients with high DcR3 level might have poor prognosis. The combined detection of AFP and DcR3 can improve the positive diagnosis ratio of HCC. It might have great significance for screening, diagnosis and prognosis of HCC by monitoring serum DcR3 levels of high-risk groups and HCC patients.
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