BMC Medical Genomics最新文献

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis and limited targeted therapies. The Hippo signaling pathway, critical in tumor progression, may harbor key genes influencing TNBC behavior. However, the specific genes and their clinical significance remain unclear.

Methods: We analyzed the GSE45827 dataset from the GEO database using differential gene expression analysis (DEG) and weighted gene co-expression network analysis (WGCNA) to identify TNBC-related genes. We enriched Hippo pathway-related genes from the MsigDB database and literature to identify candidate genes (HRGs) that may affect TNBC progression. The Boruta algorithm further screened for core genes, which were validated by immunohistochemistry in TNBC and other breast cancer tissues. Finally, we explored the biological and pharmacological significance of the target through drug prediction, molecular docking, molecular dynamics simulations, and in vitro experiments.

Results: DEG analysis identified 2,888 differentially expressed genes, and WGCNA yielded 276 TNBC-associated genes. Intersection analysis with 70 hypoxia-related genes (HRGs) revealed four key genes: TEAD4, WWTR1, AREG, and SOX11. TEAD4 was confirmed as the central gene influencing TNBC progression. Immunohistochemical results showed strong TEAD4 expression in TNBC tissues, with negligible expression in adjacent normal tissues or other breast cancer subtypes. Drug prediction and molecular docking identified irinotecan as a potential TEAD4-targeting agent. Molecular dynamics simulations confirmed the stable binding and favorable dynamics of the irinotecan-TEAD4 complex. Both TEAD4 knockdown and irinotecan treatment significantly suppressed TNBC cell migration and invasion. The combination of TEAD4 knockout and irinotecan produced a more pronounced inhibitory effect, underscoring the therapeutic potential of targeting TEAD4 in TNBC.

Conclusions: Through comprehensive analysis, we identified TEAD4 as a key gene in TNBC with high expression specificity. Irinotecan may be a potential targeted drug for TEAD4, offering a new therapeutic strategy for TNBC and potentially improving patient outcomes. Further experimental verification is required.

Background: Sjögren's syndrome (SS) is a chronic autoimmune disorder marked by lymphocytic infiltration of exocrine glands, leading to xerostomia, keratoconjunctivitis sicca, and systemic involvement including fatigue, arthralgia, and visceral organ impairment. Its pathogenesis reflects a multifactorial interaction of genetic, environmental, and hormonal influences that collectively disrupt immune homeostasis and drive tissue injury. Extensive investigations remain essential to clarify molecular pathways and establish reliable biomarkers that can enable early detection and precision therapy in SS. Detailed characterization of metabolic and molecular disturbances associated with SS is indispensable for advancing both pathophysiological insight and clinical management.

Material and methods: Rigorous quality control, batch adjustment, and data normalization were applied to untargeted metabolomics to ensure consistency and analytical reliability. Serum metabolite profiling in SS was assessed through unsupervised principal component analysis (PCA) to distinguish intergroup variations. Quantitative evaluation of metabolite abundance, machine learning-based metabolite selection, and functional enrichment analyses using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to identify candidate biomarkers. Differential gene expression and enrichment analyses, construction of protein-protein interaction (PPI) networks in the SS group, and orthogonal partial least squares discriminant analysis (OPLS-DA) were subsequently performed to investigate underlying molecular mechanisms. Correlations among metabolites, key genes, and immune cell subsets were also examined.

Results: Quality control confirmed the reliability and precision of the untargeted metabolomics data. Differential metabolite analysis highlighted significant alterations, with PC O-36:5, 4-Aminobutyric acid, and PC 16:0_16:1 exhibiting the most marked changes. Machine learning algorithms further identified metabolites including PC O-36:5, Prostaglandin B1, and L-Ergothioneine as candidates with diagnostic potential for SS. Functional enrichment revealed altered KEGG pathways including arginine and proline metabolism, pyrimidine metabolism, and nucleotide metabolism. Sequencing data analysis indicated enriched GO terms related to viral response, KEGG pathways such as Influenza A, and Gene Set Enrichment Analysis (GSEA) pathways including HUNTINGTONS_DISEASE. Two-way orthogonal partial least squares (O2PLS) delineated metabolites central to metabolic networks, such as PC O-36:5, along with genes critical to gene interaction networks, including GZMA. Correlation analysis demonstrated tight associations between metabolites, genes, and immune cell subsets in SS.

Conclusion: This integrative analysis identified molecular markers with diagnostic relevance for SS and advanced the underst

Background: Congenital biliary dilatation (CBD) is a prevalent congenital biliary disease in children, particularly in Asian populations, yet its etiology remains poorly understood. This study aimed to investigate the genome-wide DNA methylation profile in the peripheral blood of children with CBD to identify potential epigenetic mechanisms involved in its pathogenesis.

Methods: Genome-wide DNA methylation profiles were compared between whole blood samples from 37 children with CBD and 24 healthy controls using the Illumina Infinium Human MethylationEPIC (850 K) BeadChip. Bioinformatic analyses were performed to identify differentially methylated positions (DMPs) and regions (DMRs), and functional enrichment analysis was conducted on associated genes.

Results: We identified 24,230 differentially methylated sites associated with 5,863 genes. Among these, 8,313 sites were hypermethylated and 15,917 were hypomethylated in CBD patients compared to controls. 54 significant differentially methylated regions (DMRs) were also detected. Functional enrichment analysis revealed that the differentially methylated genes were significantly enriched in key biological pathways, most notably the T cell receptor signaling pathway.

Conclusion: This study presents the first comprehensive analysis of genome-wide DNA methylation in CBD, revealing significant epigenetic alterations in peripheral blood. These findings suggest that aberrant DNA methylation, particularly in genes regulating immune pathways, may play a critical role in the development of CBD and could provide valuable insights for identifying novel diagnostic biomarkers.

Background: CARS1 loss of function compound heterozygous or homozygous variants have been reported in five individuals to cause a neurodevelopmental phenotype that includes microcephaly and brittle hair and nails. Additional multisystem involvement in these five people have included neurologic, cardiac, ophthalmologic and endocrine problems.

Case presentation: We report a sixth person with novel compound heterozygous variants in CARS1. In addition to the previously reported features such as intellectual disability, neurologic features, microcephaly and hair abnormalities, this patient had persistent hypoglycemia due to congenital hyperinsulinism.

Conclusions: This report identifies two novel variants in CARS1 and expands the phenotype of this multisystem disorder to include congenital hyperinsulinism.