Objective To investigate the effects of the B7-H4 gene rs10754339 and miR-125a gene rs12976445 on cancer susceptibility through a case-control study and meta-analysis.Methods A total of 1,490 cancer patients(lung/gast...Objective To investigate the effects of the B7-H4 gene rs10754339 and miR-125a gene rs12976445 on cancer susceptibility through a case-control study and meta-analysis.Methods A total of 1,490 cancer patients(lung/gastric/liver/:550/460/480)and 800 controls were recruited in this case-control study.The meta-analysis was performed by pooling the data from previous related studies and the present study.Results The results of this study showed that in the Hubei Han Chinese population,the rs10754339gene was significantly associated with the risk of lung and gastric cancer but not liver cancer,and the rs12976445 gene was significantly associated with the risk of lung cancer but not liver or gastric cancer.The meta-analysis results indicated that rs10754339 and rs12976445 contributed to cancer susceptibility in the Chinese population and also revealed a significant association between rs10754339and breast cancer risk,as well as between rs12976445 and lung cancer risk.Conclusion The B7-H4 gene rs10754339 and miR-125a gene rs12976445 may be the potential genetic markers for cancer susceptibility in the Chinese population,which should be validated in future studies with larger sample sizes in other ethnic populations.展开更多
AIM: To investigate the expression and clinical significance of B7-H4 and hepatitis B virus X(HBx) protein in hepatitis B virus-related hepatocellular carcinoma(HBV-HCC).METHODS: The expression of B7-H4 in the human H...AIM: To investigate the expression and clinical significance of B7-H4 and hepatitis B virus X(HBx) protein in hepatitis B virus-related hepatocellular carcinoma(HBV-HCC).METHODS: The expression of B7-H4 in the human HCC cell lines Hep G2 and Hep G2.2.15 were detected by western blot, flow cytometry, and immunofluorescence. The expression of B7-H4 and HBx in 83 HBV-HCC was detected by immunohistochemistry, and the relationship with clinicopathological features was analyzed. Paraffin sections were generated from 83 HBV-HCC patients(22 females and 61 males) enrolled in this study. The age of these patients ranged from 35 to 77 years, with an average of 52.5 ± 11.3 years. All experiments were approved by the Ethics Committees of the Second Affiliated Hospital, Zhejiang University School of Medicine.RESULTS: B7-H4 was significantly upregulated in Hep G2.2.15 cells compared to Hep G2 cells. Specifically, the protein expression of B7-H4 in the lysates of Hep G2 cells was more than that in Hep G2.2.15 cells. In addition, HBx was expressed only in Hep G2.2.15 cells. Similar data were obtained by flow cytometry. The positive rates of B7-H4 and HBx in the tissues of 83 HBV-HCC patients were 68.67%(57/83) and 59.04%(49/83), respectively. The expression of HBx was correlated with tumor node metastases(TNM) stage, and the expression of B7-H4 was positively correlated with HBx(rs = 0.388; p < 0.01). The expression level of B7-H4 in HBx-positive HBV-HCC tissues was substantially higher than that in HBx-negative HBV-HCC tissues. The expression level of B7H4 was negatively related to tumor TNM stage.CONCLUSION: Higher expression of HBx and B7-H4 was correlated with tumor progression of HBV-HCC, suggesting that B7-H4 may be involved in facilitating HBV-related hepatocarcinogenesis.展开更多
B7-H4 has been shown to inhibit T cell proliferation, cytokine production and cell cycle in vitro. B7-H4 deficient mice develop exacerbated disease in the mouse models of Rheumatoid Arthritis (RA), Type 1 Diabetes (T1...B7-H4 has been shown to inhibit T cell proliferation, cytokine production and cell cycle in vitro. B7-H4 deficient mice develop exacerbated disease in the mouse models of Rheumatoid Arthritis (RA), Type 1 Diabetes (T1D) and Experimental Autoimmune Encephalomyelitis (EAE). On the other hand, B7-H4-Ig fusion protein has been documented to assuage the symptoms in mouse models of RA, T1D, and multiple sclerosis in vivo. In the present study, B7-H4-Ig bound to the majority of human peripheral blood monocytes and NK cells, but not to either normal or activated T cells. B7-H4-Ig fusion protein was assayed for its effects in allogeneic mixed lymphocyte culture (MLC) systems. Soluble B7- H4-Ig had no significant effect in the MLC, but with a tendency to promote allogeneic response. Immobilized, but not soluble B7-H4-Ig inhibited plastic bound anti-CD3 mediated activation of T cells. This inhibition however was largely due to B7-H4-Ig mediated displacement of anti-CD3 antibody from the plastic plate. Finally, B7-H4-Ig had no effect on the cytotoxicity mediated by NK and LAK cells in PBMC. Our findings thus caution against the interpretation of suppressive effect observed solely in plate-bound anti-CD3 mediated T cell co-stimulation in vitro.展开更多
Objective:To study the clinical efficacy and effect on serum HE4, SMRP, CA125, CA199, B7-H4, TPS of carboplatin combined with paclitaxel for patients with ovarian cancer.Methods:A total of 80 patients with ovarian can...Objective:To study the clinical efficacy and effect on serum HE4, SMRP, CA125, CA199, B7-H4, TPS of carboplatin combined with paclitaxel for patients with ovarian cancer.Methods:A total of 80 patients with ovarian cancer in our hospital from December 2014 to December 2016 were enrolled in this study. The subjects were divided into the control group (n=40) and the treatment group (n=40) randomly. The control group was treated with carboplatin;the treatment group was treated with carboplatin combined with paclitaxel. 21 d for a period of treatment and the two groups were treated for 2 periods. The serum HE4, SMRP, CA125, CA199, B7-H4, TPS levels of the two groups before and after treatment was compared. Results:There were no significantly differences of the serum HE4, SMRP, CA125, CA199, B7-H4, TPS levels of the two groups before treatment. The serum HE4, SMRP, CA125, CA199, B7-H4, TPS levels of the two groups after treatment were significantly lower than before treatment, and that of the treatment group were significantly lower than that of the control group.Conclusion: Carboplatin combined with paclitaxe for patients with ovarian cancer can significantly reduce the serum HE4, SMRP, CA125, CA199, B7-H4, TPS levels;can be used for the prognosis of patients with ovarian cancer after treatment.展开更多
目的:本研究旨在评估FAS和B7-H4在重度子痫前期(sPE)中的诊断价值及其对围产期不良心血管结局的预测价值。方法:使用GEO2R在线工具分析GSE2347219数据集。收集60例健康孕妇和60名sPE患者,并收集血清。通过RT-qPCR分析血清B7-H4和FAS的...目的:本研究旨在评估FAS和B7-H4在重度子痫前期(sPE)中的诊断价值及其对围产期不良心血管结局的预测价值。方法:使用GEO2R在线工具分析GSE2347219数据集。收集60例健康孕妇和60名sPE患者,并收集血清。通过RT-qPCR分析血清B7-H4和FAS的表达水平。通过直接ROC分析评估FAS和B7-H4分别对sPE的诊断价值和不良心血管结局的预测价值。通过二元logistics回归分析因子预测概率值,然后进行ROC分析,评估AS和B7-H4联合对sPE的诊断价值和不良心血管结局的预测价值。使用sPE血清培养心肌细胞,检测细胞中的肥大因子和纤维化因子。结果:GSE2347219数据集分析结果显示,FAS和B7-H4在sPE胎盘组织中上调。血清检测结果表明,FAS和B7-H4在sPE血清中上调。直接ROC分析结果表明,FAS和B7-H4可以区分sPE病例与正常孕妇,而且可以预测不良心血管结局。二元logistics回归分析和ROC分析结果表明,B7-H4联合FAS可以有效地区分sPE病例与正常孕妇并有效预测不良心血管结局。sPE血清培养可以升高心肌细胞中的肥大因子(ANP、BNP和β-MHC)和纤维化因子COL1A1的水平。结论:B7-H4 (VTCN1)联合FAS可以作为sPE患者的诊断因子和不良心血管结局的预测因子。Objective: The aim of this study was to evaluate the diagnostic value of FAS and B7-H4 in severe preeclampsia (sPE) and its predictive value for adverse perinatal cardiovascular outcomes. Methods: The GSE2347219 dataset was analyzed using the GEO2R online tool. Sixty healthy pregnant women and sixty patients who were sPE were collected and serum was collected. The expression levels of serum B7-H4 and FAS were analyzed by RT-qPCR. The diagnostic value of FAS and B7-H4 for sPE and the predictive value of adverse cardiovascular outcomes were assessed by direct ROC analysis. Predictive probability values were analyzed by binary logistics regression followed by ROC analysis to assess the diagnostic value and predictive value of adverse cardiovascular outcomes of combined FAS and B7-H4. Cardiomyocytes were cultured using sPE serum, and hypertrophic and fibrotic factors were detected in the cells. Results: Analysis of GSE2347219 dataset showed that FAS and B7-H4 were upregulated in sPE placental tissues. Serum assay results indicated that FAS and B7-H4 were upregulated in sPE serum. Direct ROC analysis showed that FAS and B7-H4 could distinguish sPE cases from normal pregnant women and that they could predict adverse cardiovascular outcomes. Binary logistic regression analysis and ROC analysis showed that B7-H4 in combination with FAS could effectively differentiate sPE cases from normal pregnant women and effectively predict adverse cardiovascular outcomes. sPE serum culture elevated the levels of hypertrophic factors (ANP, BNP, and β-MHC) and fibrosis factor COL1A1 in cardiomyocytes. Conclusion: B7-H4 (VTCN1) in combination with FAS can be used as a diagnostic factor and predictor of adverse cardiovascular outcomes in patients with sPE.展开更多
基金supported by the Fundamental Research Funds for the Central Universities (WUT:2020IB029)。
文摘Objective To investigate the effects of the B7-H4 gene rs10754339 and miR-125a gene rs12976445 on cancer susceptibility through a case-control study and meta-analysis.Methods A total of 1,490 cancer patients(lung/gastric/liver/:550/460/480)and 800 controls were recruited in this case-control study.The meta-analysis was performed by pooling the data from previous related studies and the present study.Results The results of this study showed that in the Hubei Han Chinese population,the rs10754339gene was significantly associated with the risk of lung and gastric cancer but not liver cancer,and the rs12976445 gene was significantly associated with the risk of lung cancer but not liver or gastric cancer.The meta-analysis results indicated that rs10754339 and rs12976445 contributed to cancer susceptibility in the Chinese population and also revealed a significant association between rs10754339and breast cancer risk,as well as between rs12976445 and lung cancer risk.Conclusion The B7-H4 gene rs10754339 and miR-125a gene rs12976445 may be the potential genetic markers for cancer susceptibility in the Chinese population,which should be validated in future studies with larger sample sizes in other ethnic populations.
基金Supported by the National Natural Science Foundation of China,No.81272679 and No.81470851Zhejiang Provincial Natural Science Foundation of China,No.LQ16H160005 and No.LY15H080002+1 种基金the Medical Science and Technology Project of Zhejiang Province,No.201337756the Educational Commission of Zhejiang Province of China,No.Y201328079
文摘AIM: To investigate the expression and clinical significance of B7-H4 and hepatitis B virus X(HBx) protein in hepatitis B virus-related hepatocellular carcinoma(HBV-HCC).METHODS: The expression of B7-H4 in the human HCC cell lines Hep G2 and Hep G2.2.15 were detected by western blot, flow cytometry, and immunofluorescence. The expression of B7-H4 and HBx in 83 HBV-HCC was detected by immunohistochemistry, and the relationship with clinicopathological features was analyzed. Paraffin sections were generated from 83 HBV-HCC patients(22 females and 61 males) enrolled in this study. The age of these patients ranged from 35 to 77 years, with an average of 52.5 ± 11.3 years. All experiments were approved by the Ethics Committees of the Second Affiliated Hospital, Zhejiang University School of Medicine.RESULTS: B7-H4 was significantly upregulated in Hep G2.2.15 cells compared to Hep G2 cells. Specifically, the protein expression of B7-H4 in the lysates of Hep G2 cells was more than that in Hep G2.2.15 cells. In addition, HBx was expressed only in Hep G2.2.15 cells. Similar data were obtained by flow cytometry. The positive rates of B7-H4 and HBx in the tissues of 83 HBV-HCC patients were 68.67%(57/83) and 59.04%(49/83), respectively. The expression of HBx was correlated with tumor node metastases(TNM) stage, and the expression of B7-H4 was positively correlated with HBx(rs = 0.388; p < 0.01). The expression level of B7-H4 in HBx-positive HBV-HCC tissues was substantially higher than that in HBx-negative HBV-HCC tissues. The expression level of B7H4 was negatively related to tumor TNM stage.CONCLUSION: Higher expression of HBx and B7-H4 was correlated with tumor progression of HBV-HCC, suggesting that B7-H4 may be involved in facilitating HBV-related hepatocarcinogenesis.
文摘B7-H4 has been shown to inhibit T cell proliferation, cytokine production and cell cycle in vitro. B7-H4 deficient mice develop exacerbated disease in the mouse models of Rheumatoid Arthritis (RA), Type 1 Diabetes (T1D) and Experimental Autoimmune Encephalomyelitis (EAE). On the other hand, B7-H4-Ig fusion protein has been documented to assuage the symptoms in mouse models of RA, T1D, and multiple sclerosis in vivo. In the present study, B7-H4-Ig bound to the majority of human peripheral blood monocytes and NK cells, but not to either normal or activated T cells. B7-H4-Ig fusion protein was assayed for its effects in allogeneic mixed lymphocyte culture (MLC) systems. Soluble B7- H4-Ig had no significant effect in the MLC, but with a tendency to promote allogeneic response. Immobilized, but not soluble B7-H4-Ig inhibited plastic bound anti-CD3 mediated activation of T cells. This inhibition however was largely due to B7-H4-Ig mediated displacement of anti-CD3 antibody from the plastic plate. Finally, B7-H4-Ig had no effect on the cytotoxicity mediated by NK and LAK cells in PBMC. Our findings thus caution against the interpretation of suppressive effect observed solely in plate-bound anti-CD3 mediated T cell co-stimulation in vitro.
基金Young Fund of Hubei Natural Science Foundation of China(2016CFB340)Basic Research Project of Wuhan Science and Technology Bureau(NO.2015061701011626)Key Project of Wuhan Municipal Health and Family Planning Commission(NO.WX15A08).
文摘Objective:To study the clinical efficacy and effect on serum HE4, SMRP, CA125, CA199, B7-H4, TPS of carboplatin combined with paclitaxel for patients with ovarian cancer.Methods:A total of 80 patients with ovarian cancer in our hospital from December 2014 to December 2016 were enrolled in this study. The subjects were divided into the control group (n=40) and the treatment group (n=40) randomly. The control group was treated with carboplatin;the treatment group was treated with carboplatin combined with paclitaxel. 21 d for a period of treatment and the two groups were treated for 2 periods. The serum HE4, SMRP, CA125, CA199, B7-H4, TPS levels of the two groups before and after treatment was compared. Results:There were no significantly differences of the serum HE4, SMRP, CA125, CA199, B7-H4, TPS levels of the two groups before treatment. The serum HE4, SMRP, CA125, CA199, B7-H4, TPS levels of the two groups after treatment were significantly lower than before treatment, and that of the treatment group were significantly lower than that of the control group.Conclusion: Carboplatin combined with paclitaxe for patients with ovarian cancer can significantly reduce the serum HE4, SMRP, CA125, CA199, B7-H4, TPS levels;can be used for the prognosis of patients with ovarian cancer after treatment.
文摘目的:本研究旨在评估FAS和B7-H4在重度子痫前期(sPE)中的诊断价值及其对围产期不良心血管结局的预测价值。方法:使用GEO2R在线工具分析GSE2347219数据集。收集60例健康孕妇和60名sPE患者,并收集血清。通过RT-qPCR分析血清B7-H4和FAS的表达水平。通过直接ROC分析评估FAS和B7-H4分别对sPE的诊断价值和不良心血管结局的预测价值。通过二元logistics回归分析因子预测概率值,然后进行ROC分析,评估AS和B7-H4联合对sPE的诊断价值和不良心血管结局的预测价值。使用sPE血清培养心肌细胞,检测细胞中的肥大因子和纤维化因子。结果:GSE2347219数据集分析结果显示,FAS和B7-H4在sPE胎盘组织中上调。血清检测结果表明,FAS和B7-H4在sPE血清中上调。直接ROC分析结果表明,FAS和B7-H4可以区分sPE病例与正常孕妇,而且可以预测不良心血管结局。二元logistics回归分析和ROC分析结果表明,B7-H4联合FAS可以有效地区分sPE病例与正常孕妇并有效预测不良心血管结局。sPE血清培养可以升高心肌细胞中的肥大因子(ANP、BNP和β-MHC)和纤维化因子COL1A1的水平。结论:B7-H4 (VTCN1)联合FAS可以作为sPE患者的诊断因子和不良心血管结局的预测因子。Objective: The aim of this study was to evaluate the diagnostic value of FAS and B7-H4 in severe preeclampsia (sPE) and its predictive value for adverse perinatal cardiovascular outcomes. Methods: The GSE2347219 dataset was analyzed using the GEO2R online tool. Sixty healthy pregnant women and sixty patients who were sPE were collected and serum was collected. The expression levels of serum B7-H4 and FAS were analyzed by RT-qPCR. The diagnostic value of FAS and B7-H4 for sPE and the predictive value of adverse cardiovascular outcomes were assessed by direct ROC analysis. Predictive probability values were analyzed by binary logistics regression followed by ROC analysis to assess the diagnostic value and predictive value of adverse cardiovascular outcomes of combined FAS and B7-H4. Cardiomyocytes were cultured using sPE serum, and hypertrophic and fibrotic factors were detected in the cells. Results: Analysis of GSE2347219 dataset showed that FAS and B7-H4 were upregulated in sPE placental tissues. Serum assay results indicated that FAS and B7-H4 were upregulated in sPE serum. Direct ROC analysis showed that FAS and B7-H4 could distinguish sPE cases from normal pregnant women and that they could predict adverse cardiovascular outcomes. Binary logistic regression analysis and ROC analysis showed that B7-H4 in combination with FAS could effectively differentiate sPE cases from normal pregnant women and effectively predict adverse cardiovascular outcomes. sPE serum culture elevated the levels of hypertrophic factors (ANP, BNP, and β-MHC) and fibrosis factor COL1A1 in cardiomyocytes. Conclusion: B7-H4 (VTCN1) in combination with FAS can be used as a diagnostic factor and predictor of adverse cardiovascular outcomes in patients with sPE.
