Comparative and Functional Genomics最新文献

B-cell chronic lymphocytic leukemia (B-CLL) is the most common hematological malignancy in adults. Its clinical course is heterogeneous, ranging from indolent forms with slow progression to aggressive variants refractory to conventional treatment. In recent years, it has been shown that epigenetic alterations, such as DNA methylation, histone modifications, and regulation by noncoding RNAs, especially microRNAs (miRNAs), play a central role in the prognosis of this disease. For this reason, the analysis of epigenetic mechanisms has become an essential approach both to understand the progression of B-CLL and to predict therapeutic response and patient survival.

Colorectal cancer (CRC) is one of the most common malignancies of the digestive tract globally, characterized by high incidence, difficulty in early diagnosis, and poor prognosis. Traditional screening methods have limitations in sensitivity and specificity, thus necessitating the development of novel, efficient molecular diagnostic approaches. Recent studies have highlighted the crucial role of mitochondrial dysfunction in the initiation and progression of various cancers, suggesting that mitochondria-related genes (MRGs) could serve as promising diagnostic targets for CRC. In this study, we integrated transcriptomic data from 1174 samples across The Cancer Genome Atlas (TCGA) and multiple Gene Expression Omnibus (GEO) public datasets (GSE21510, GSE44076, and GSE9348) and combined it with MRG data from the MitoCarta3.0 database for a systematic analysis of differentially expressed genes (DEGs). Using LASSO regression and SVM-RFE, two machine learning algorithms, we identified eight key MRGs (ABCG2, ANK2, MACC1, PMAIP1, SLC22A5, SLC25A34, ACAT1, and PDK4) and constructed an early diagnostic model for CRC. Receiver operating characteristic (ROC) curve analysis confirmed the diagnostic efficacy of the model. Gene interaction networks were constructed using GeneMANIA, demonstrating the potential synergistic roles of these genes in regulating cellular metabolism, drug efflux, and immune modulation. CIBERSORT immune cell infiltration analysis revealed significant correlations between these genes and various immune cell subtypes, including T cells, macrophages, and dendritic cells. Further integration of single-cell RNA sequencing data (GSE245552) identified the specific expression patterns of the diagnostic model genes across different cell types. Additionally, we conducted an in-depth investigation of the ANK2 gene. Immunohistochemistry (HPA database), qRT-PCR, and western blotting confirmed the significantly low expression of ANK2 in CRC tissues and cell lines. Moreover, TUNEL and angiogenesis assays showed that overexpression of ANK2 significantly promoted cell apoptosis and inhibited angiogenesis, suggesting that ANK2 may function as a key tumor suppressor in CRC. In conclusion, this study proposes and validates a CRC diagnostic model based on differentially expressed mitochondrial genes. We systematically explored the molecular mechanisms and immune microenvironment correlations of the model and confirmed the biological effects through single-cell and molecular biology experiments. Notably, we highlight the potential regulatory role of ANK2 in the progression of CRC. This research provides theoretical support and new directions for early screening, diagnostic biomarker identification, and targeted therapy strategies for CRC.

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, primarily due to metastatic progression and an immunosuppressive tumor immune microenvironment (TIME). The stress-responsive gene IER3 is found to be dysregulated in multiple cancers. Currently, its functional role in CRC pathogenesis and immune modulation remains poorly understood. Here, using integrated single-cell RNA sequencing (scRNA-seq) of clinical samples, we identify a distinct IER3-expressing malignant subpopulation associated with aggressive disease and poor prognosis. Functional studies demonstrate that IER3 drives CRC proliferation, invasion, and metastatic capacity both in vitro and in vivo. Mechanistically, IER3 activates the TNF-α/NF-κB signaling pathway, thereby enhancing the expression and phosphorylation of RELA/p65. Moreover, IER3⁺ malignant cells reshape the TIME into an immunosuppressive state by altering immune cell infiltration and promoting communication via the FN1–CD44 axis. High IER3 expression correlates with reduced response to immune checkpoint blockade (ICB) and distinct drug sensitivity profiles. Together, these findings confirm that IER3 is a dual critical mediator of CRC progression and immune escape, highlighting its potential as a therapeutic target and biomarker for personalized treatment strategies.

Klebsiella pneumoniae is a Gram-negative, facultatively anaerobic member of the Enterobacteriaceae that functions both as a gut commensal and a major opportunistic pathogen implicated in severe hospital and community-acquired infections. The rapid global expansion of antimicrobial-resistant K. pneumoniae lineages, particularly ESBL- and carbapenemase-producing strains, poses an escalating public health threat by eroding available treatment options. This study investigated the genomic architecture and resistance mechanisms of K. pneumoniae isolates recovered from urinary tract infections, wound infections, and cervical cancer cases across Ghana, Togo, and Benin. Eight isolates were subjected to antimicrobial susceptibility profiling and whole genome sequencing using the Illumina MiSeq platform after DNA extraction via the Zymo protocol. Comprehensive genomic analyses including MLST, resistance gene detection (Abricate), phylogenetic reconstruction (iTOL), genomic island prediction (IslandViewer), genome structural analysis (Proksee), and statistical interrogation in R (v4.4.0) were performed to characterize genetic diversity and identify determinants of antimicrobial resistance. The isolates exhibited heterogeneous but overlapping resistance profiles, extensive carriage of AMR genes, and the presence of multiple genomic islands enriched for integrases, transposases, and antibiotic resistance cassettes. MLST and SNP-based comparisons revealed both clonal clusters and genetically divergent lineages, while recombination analysis indicated mutation-driven evolution with lineage-specific recombination hotspots. Conserved gene orientation patterns and regions of atypical GC content further suggested historical acquisition of mobile genetic elements, including plasmid integrations and resistance islands. Collectively, these findings demonstrate the high genomic plasticity, multidrug-resistant phenotypes, and dynamic evolutionary processes shaping K. pneumoniae populations circulating in West Africa. The study underscores the urgent need for continuous regional genomic surveillance to guide treatment policies and limit the further dissemination of high-risk AMR clones.

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, with tumor microenvironment (TME) heterogeneity playing a critical role in disease progression and therapeutic response. Immune escape (IE) mechanisms facilitate tumor evasion from host immune surveillance, yet their characterization at the single-cell level in CRC is incomplete. This study integrated single-cell RNA sequencing (scRNA-seq) and bulk transcriptomic data from multiple public cohorts to systematically explore IE-related signatures in CRC. We identified major and minor cell populations within the TME and performed differential gene expression analysis. Using high-dimensional weighted gene coexpression network analysis (hdWGCNA), we identified gene modules correlated with IE activity. Subsequent survival analysis across six independent cohorts revealed Gamma-glutamylcyclotransferase (GGCT) as a novel prognostic biomarker associated with poor survival. Functional enrichment analysis indicated GGCT′s involvement in critical oncogenic pathways. Furthermore, GGCT expression correlated with altered immune infiltration profiles and stromal components, suggesting its role in modulating the immunosuppressive TME. Additionally, GGCT demonstrated potential predictive value for response to immunotherapy across multiple datasets. Our findings highlight GGCT as a key player in CRC immune evasion and a promising therapeutic target.