Increased serum and ascitic fluid levels of soluble tumor necrosis factor-p55 in hepatocellular carcinoma patients

Objective: To explore the levels of serum and ascitic fluid soluble tumor necrosis factor receptor-p55 (sTNFR-p55) and understand their clinical implication in primary hepatocellular carcinoma (HCC) patients. Methods: Enzyme-linked immunosorbent assay (ELISA) was used to examine the levels of sTNFR-p55 in the serum and ascitic fluid in 25 HCC patients and 25 patients with liver cirrhosis (LC). The test was also performed on the serum of 30 healthy subjects who served as control group. To assess the clinical effects of increased serum concentrations of sTNFR-p55, four parameters were analyzed by logistic regression. Results: Serum and ascitic fluid levels of sTNFR-p55 in HCC patients were significantly higher than those in LC patients and controls (P=0. 001). No significant difference was found between serum sTNFR-p55 levels in the latter 2 groups (P = 0. 19), and positive correlation between serum levels of sTNFR-p55 and that in ascitic fluid was noted in the 2 patient groups (r=1. 000, P<0. 001). Levels of the sTNFR-p55 positively correlated with TBIL and AFP in the peripheral blood of HCC patients (r=0. 524, P = 0. 01 and r=0. 234, P = 0. 03, respectively). Conclusion: Increased levels of sTNFRs-p55 in the serum and ascitic fluid could reflect the abnormal immune status of the HCC patients and may help predict the development of the tumor.

Increase of tumor necrosis factor receptor 1 expression in women with unexplained early spontaneous abortion

Objective: To investigate membrane tumor necrosis factor receptor 1 protein expression level in decidua and concentration of soluble tumor necrosis factor receptor 1 in serum in women with unexplained early spontaneous abortion, threatened abortion, and compare the levels with healthy pregnant women. Methods: Thirty-seven women with unexplained early spontaneous abortion, 27 women with threatened abortion, and 34 healthy pregnant women undergoing artificial abortion of pregnancy at 6 - 10 weeks of gestation were selected. Decidual samples were collected when women were undergoing artificial abortion, and blood samples were collected at the same time. The level of membrane tumor necrosis factor receptor 1 in decidua was detected by flow cytometer, and the concentration of soluble tumor necrosis factor receptor 1 in sera was measured with an enzyme-linked immunosorbent assay. Results: The percentages of membrane tumor necrosis factor receptor 1 positive decidual cells were 16.42 ± 7.10 Mean ± SD for women with unexplained early spontaneous abortion and 13. 14 ± 6.30 for healthy pregnant women ( P < 0.05). Serum concentration of soluble tumor necrosis factor receptor 1 was significantly higher in women with unexplained early spontaneous abortion than in healthy pregnant women and in women with threatened abortion, and no difference was found between healthy pregnant women and women with threatened abortion. Conclusion: Women with unexplained early spontaneous abortion present significantly higher expression of tumor necrosis factor receptor 1 than healthy pregnant women, suggesting that over-expression of tumor necrosis factor receptor 1 may contribute to the development of early spontaneous abortion.

Early detection of hepatocellular carcinoma co-occurring with hepatitis C virus infection: A mathematical model

AIM: To develop a mathematical model for the early detection of hepatocellular carcinoma (HCC) with a panel of serum proteins in combination with α-fetoprotein (AFP).METHODS: Serum levels of interleukin (IL)-8, soluble intercellular adhesion molecule-1 (sICAM-1), soluble tumor necrosis factor receptor II (sTNF-RII), proteasome, and β-catenin were measured in 479 subjects categorized into four groups: (1) HCC concurrent with hepatitis C virus (HCV) infection (n = 192); (2) HCV related liver cirrhosis (LC) (n = 96); (3) Chronic hepatitis C (CHC) (n = 96); and (4) Healthy controls (n = 95). The R package and different modules for binary and multi-class classifiers based on generalized linear models were used to model the data. Predictive power was used to evaluate the performance of the model. Receiver operating characteristic curve analysis over pairs of groups was used to identify the best cutoffs differentiating the different groups.RESULTS: We revealed mathematical models, based on a binary classifier, made up of a unique panel of serum proteins that improved the individual performance of AFP in discriminating HCC patients from patients with chronic liver disease either with or without cirrhosis. We discriminated the HCC group from the cirrhotic liver group using a mathematical model (-11.3 + 7.38 × Prot + 0.00108 × sICAM + 0.2574 × β-catenin + 0.01597 × AFP) with a cutoff of 0.6552, which achieved 98.8% specificity and 89.1% sensitivity. For the discrimination of the HCC group from the CHC group, we used a mathematical model [-10.40 + 1.416 × proteasome + 0.002024 × IL + 0.004096 × sICAM-1 + (4.251 × 10-4) × sTNF + 0.02567 × β-catenin + 0.02442 × AFP] with a cutoff 0.744 and achieved 96.8% specificity and 89.7% sensitivity. Additionally, we derived an algorithm, based on a binary classifier, for resolving the multi-class classification problem by using three successive mathematical model predictions of liver disease status.CONCLUSION: Our proposed mathematical model may be a useful method for the early detection of different statuses of liver disease co-occurring with HCV infection.