Accuracy of analysis of cfDNA for detection of single nucleotide variants and copy number variants in breast cancer.

BACKGROUND: Gene variants are dependable and sensitive biomarkers for target-specific therapies in breast cancer (BC). However, detection of mutations within tissues has many limitations. Plasma circulating free DNA (cfDNA) has been reported in many studies as an alternative tool for detection of mutations. But the diagnostic accuracy of cfDNA for most mutations in BC needs to be reviewed. This study was designed to perform comparative assessment of the diagnostic performance of cfDNA and DNA extracted from tissues for detection of single nucleotide variants (SNV) and copy number variants (CNV). METHODS: True-positive (TP), false-positive (FP), false-negative (FN), and true-negative (TN) values were extracted from each selected study. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated. Subgroup analysis and single study omitted analysis were performed to quantify and explain the study heterogeneity. RESULTS: Twenty eligible studies that involved 1055 cases were included in this meta-analysis. SNV studies in early breast cancer (EBC) subgroup are not suitable for meta-analysis owing to high heterogeneity. However, in advanced breast cancer (ABC) subgroup, the pooled sensitivity and specificity of detection of SNVs were 0.78 (0.71-0.84) and 0.92 (0.87-0.95), respectively. The summary receiver operative curve (SROC) exhibited an area under the curve (AUC) of 0.91(0.88-0.93). The pooled results of studies involving subgroups of PIK3CA, TP53, and ESR1 indicate that the diagnostic value of different genes is different, such as AUC for PIK3CA and TP53 were reported to be 0.96 (0.94-0.98) and 0.94 (0.91-0.95), respectively, and ESR1 had the lowest diagnostic value of 0.80 (0.76-0.83). Owing to the low sensitivity and AUC in the cases of CNV, there is no value for cfDNA-based detection of CNV based on insufficient amount of CNV data. CONCLUSION: This meta-analysis suggests that the detection of gene mutations in cfDNA have adequate diagnostic accuracy and can be used as an alternative to the tumor tissue for detection of SNV but not for CNV in BC yet.

Antibodies: The major participants in maternal-fetal interaction.

The aim of this study is to improve our understanding of the mechanisms involved in maternal-fetal immune tolerance. We searched the related literatures and overviewed the major antibodies associated with pregnancy and described in details their possible roles in mediating maternal-fetal interactions. Antibodies classified into different types based on their functional or structural characteristics were summarized, including immunoglobulin G, blocking antibody, nonprecipitating asymmetric antibody, antiphospholipid antibody, antitrophoblast antibody and antipaternal antibody. The presence and levels of various circulating antibodies in pregnancy may play a crucial role in the occurrence, development and termination of pregnancy.

Association between CD14 gene promoter polymorphisms with serum total-IgE and eosinophil levels in atopic and non-atopic asthma patients in a Chinese Han population.

OBJECTIVE: The aim of this study was to investigate the association between CD14 gene promoter SNPs with serum total-IgE and eosinophil levels in atopic asthma and non-atopic asthma in Chinese Han. METHODS: A total of 152 patients with asthma were divided into atopic asthma (n = 100) and non-atopic asthma (n = 52) groups for this study. Six CD14 gene SNPs were analyzed using PCR and gene sequencing. Serum total-IgE and eosinophil levels were measured. The association between genotype frequencies of the CD14 gene loci with total-IgE and eosinophil levels in atopic asthma and non-atopic asthma was evaluated by the ANOVA test method. Hundred and sixteen healthy subjects constitute the control group. RESULTS: We found that serum total-IgE and eosinophil levels were significantly higher in individuals with atopic asthma when compared to individuals with non-atopic asthma (p < 0.01). For non-atopic asthma, the total-IgE levels of the heterozygous genotypes were significantly higher than the corresponding levels for the homozygous genotypes in CD14-260C > T, CD-651C > T, CD-911A > C and CD-1247A > G (p < 0.01). In atopic asthma, there was no statistical significance for either serum total-IgE or eosinophil levels among the genotypes of the CD14 gene SNPs. In addition, allele A frequency of CD14-1247A > G was significantly different between the atopic asthma and non-atopic asthma groups (p = 0.025). CONCLUSIONS: There was a statistical association between the serum total-IgE level and the CD14 gene promoter SNPs in the non-atopic asthma group. The eosinophil level was not found to be statistically associated with the CD14 gene promoter SNPs in either the atopic asthma or non-atopic asthma groups.