Anti-FCGR2A monoclonal antibody, clone AT10

Background: In recent studies, microRNAs have been demonstrated as stable detectable biomarkers in blood for cancer. In addition, computer-aided biomarker discovery has now become an attractive paradigm for precision diagnosis. Methods: In this study, we identified and evaluated miR-139-3p as a biomarker for screening of esophageal squamous cell carcinoma using the Cancer Genome Atlas and Gene Expression Omnibus database analyses. We identified possible miR-139-3p target genes through the predicted database and esophageal squamous cell carcinoma upregulated genes from the Cancer Genome Atlas and Gene. Bioinformatics analysis was performed to determine key miR-139-3p targets and pathways associated with esophageal carcinoma. Finally, the expression and expected significance of hub genes were evaluated via the Genotype-Tissue Expression project. Results: MiR-139-3p was significantly downregulated in patients with esophageal squamous cell carcinoma/esophageal carcinoma. In GSE 122497, the area under the curve-receiver operating characteristic value, sensitivity, and specificity for serum miR-139-3p were 0.754, 67.49%, and 80.00%, respectively. The pattern specification process, skeletal system development, and regionalization process were the most enriched interactions in esophageal carcinoma. In addition, Epstein-Barr virus infection, human T-cell leukemia virus 1 infection, and human cytomegalovirus infection were identified as crucial pathways. Six hub genes (CD1A, FCGR2A, ANPEP, CD1B, membrane metalloendopeptidase, and TWIST1) were found, and FCGR2A and membrane metalloendopeptidase were further confirmed by genotype-tissue expression. High expression of membrane metalloendopeptidase correlated with a better overall survival but not with disease-free survival of patients with esophageal carcinoma. Conclusions: MiR-139-3p was identified as a candidate biomarker for predicting esophageal squamous cell carcinoma based on network analysis. MiR-139-3p acted as a tumor suppressor by targeting membrane metalloendopeptidase in esophageal carcinoma, and low expression of membrane metalloendopeptidase may indicate a better prognosis of patients with esophageal carcinoma.

Background Severe malarial anaemia is a major cause of mortality from malaria. Although of enormous relevance, its pathogenesis is largely unknown. Interestingly, the extent of anaemia greatly exceeds the loss of erythrocytes due to direct destruction by the pathogen Plasmodium falciparum. Immune response against the parasite is partially mediated through the Fc receptor for immunoglobulin (Ig) G IIa (Fc gamma RIIa, CD32). The presence of an arginine instead of a histidine residue at amino acid position 131 (H131R) in the extracellular domain of Fc gamma RIIa reduces the affinity of the receptor for IgG(2) and IgG(3) isotypes but increases the binding activity for C reactive protein (CRP). Methods In Ghana, West Africa, 2504 children with severe malaria and 2027 matched healthy controls were studied for the Fc gamma RIIa(H131R) polymorphism in order to ascertain its influence on major manifestations of the disease. The study group included patients with partly overlapping symptoms of severe malaria, among them 1591 cases with severe anaemia, 562 cases with cerebral malaria, and 497 cases with other malaria complications. Results Analyses of the genotype distributions indicated that, under a recessive model, Fc gamma RIIa(131RR) was positively associated with severe malaria collectively (OR 1.20, 95% CI 1.05 to 1.38; p = 0.007, p(corrected) = 0.021) and, after stratification for phenotypes, with severe anaemia (OR 1.33, 95% CI 1.13 to 1.57; p = 0.001, p(corrected) = 0.009), but not with cerebral malaria (OR 1.04, 95% CI 0.82 to 1.33; p = 0.733) or other malaria complications (OR 1.03, 95% CI 0.78 to 1.37; p = 0.827). No association was found with levels of parasitaemia. Conclusion The positive association with a CRP binding variant of Fc gamma RIIa supports evidence for a role of CRP mediated defence mechanisms in the pathogenesis of severe malarial anaemia.