ObjectiveTo summarize the correlation between human epidermal growth factor receptor 2 (HER2) gene expression and the efficacy of targeted therapy for patients with HER2-positive breast cancer, and to summarize the new progress in the study of HER2 gene copy number. MethodThe relevant literatures on researches of targeted therapy effectiveness for patients with HER2-positive breast cancer were retrieved and reviewed. ResultsHER2 gene copy number and HER2/centromere on chromosome 17 (CEP17) ratio were related to the prognosis of patients with HER2-positive breast cancer, and circulating tumor DNA sequencing was expected to be a predictive indicator of targeted therapy effectiveness. ConclusionHigher copy number of HER2 gene might be associated with a better prognosis of HER2-positive breast cancer, and HER2/CEP17 ratio and circulating tumour DNA are of some significances in evaluating treatment response of trastuzumab for patients with HER2-positive breast cancer.
ObjectiveTo analyze the single nucleotide polymorphism (SNP) and the copy number variation (CNV) of cardiac tumors to find the SNP sites and CNV events that may play important roles in the occurrence of tumors. MethodsThe patients with myxoma admitted to our hospital from 2015 to 2019 were randomly selected. The SNP analysis and the CNV test in gene level were performed through whole exome sequencing (WES). The samples were divided into two groups according to the mean size of the tumor: a diameter≤5.7 cm group and a dimeter>5.7 cm group. The analysis results were compared between the two groups. ResultsA total of 14 patients were enrolled, including 8 females and 6 males with a mean age of 61.4 (41-79) years. Thirty-seven cancer-genes with SNP were detected, among which 18 mutated sites had a mutation rate of>10%; and TP53, EP300 and CREBBP played a core binding role in protein-protein interaction-network. The GO enrichment results showed significant differences in the regulation of cell secretion of the mutated genes, and the KEGG enrichment results showed significant differences in the PI3K-AKT and JAK-STAT signaling pathways in the occurrence of myxoma. In addition, 17 new mutation sites of tumor genes with high mutation effect were found in SNP detection. The WES results of 14 samples showed that the CNV events were detected in 120 tumor genes of the samples, 10 of which were included in two tumor databases. The GO enrichment results showed significant differences in the tube development and regulation of cell proliferation, and the KEGG enrichment results showed significant differences in the comprehensive tumor signaling pathway. Statistical differences of ERCC6L and INTS6L in CNV test were found (P<0.05). ConclusionThere may be multiple tumor gene site mutations in the process of tumor generation, among which there are multiple core tumor genes such as TP53, EP300 and CREB, which regulate tumor cells through PI3K-AKT and JAK-STAT signaling pathways and play an important role in tumor generation. The CNV of ERCC6L and INTS6L genes may be related to tumor growth.
Objective To explore the causal relationship between DNA copy number and the risk of Alzheimer disease (AD) using Mendelian randomization (MR) methods, as well as to investigate the potential mediating effects of immune cells. Methods The data related to 731 immune cell types, DNA copy number and AD from the Genome-Wide Association Study database were collected. A bidirectional MR analysis was conducted to explore the causal relationship between DNA copy number and AD, primarily using the inverse-variance weighted method and MR-Egger method. Additionally, a two-step mediation analysis was performed to identify potential mediating immune cells. Results A total of 134 single-nucleotide polymorphisms were included for bidirectional MR analysis. The MR methods results showed a negative causal relationship between DNA copy number and the risk of AD (P<0.05), while the reverse analysis showed no statistical significance. Sensitivity analysis confirmed the robustness of these results. The mediation analysis indicated that the immune cell phenotype (HVEM on CD45RA-CD4+) partially mediated the causal relationship between DNA copy numbers and the risk of AD, with a mediation effect proportion of 4.6%. Conclusion An increase in DNA copy numbers may reduce the risk of AD, and immune cells partially mediate this causal relationship.