Your browser does not allow saving data (e.g. private mode): bookmarks will be lost when the tab closes.
Search PubMed
Keywords, author, journal, years — results from PubMed, abstracts with Russian translation, bookmarks in your browser.
Found: 4 944
Page 421 of 495-
Fibulin-5 (FBLN5) as a context-dependent pan-cancer regulator: integrated multi-omics analysis reveals dual roles in tumor progression and therapeutic resistance.
BACKGROUND: Fibulin-5 (FBLN5) is a key member of the extracellular matrix (ECM), which plays an important role in the occurrence and development of tumors. This study aimed to determine the role of FBLN5 in the diagnosis, prognosis, and immune regulation of tumors using a pan-cancer analysis. METHODS: By integrating and analyzing data from multiple public databases, including The Cancer Genome Atlas (TCGA), Firehose, University of California, Santa Cruz (UCSC) Xena, cBioPortal, Gene Expression Omnibus (GEO), Clinical Proteomic Tumor Analysis Consortium (CPTAC), Tumor Immune Estimation Resource 2.0 (TIMER2.0), Tumor Immune Single-cell Hub (TISCH), CellMiner, Genomics of Drug Sensitivity in Cancer (GDSC), and Cancer Therapeutics Response Portal (CTRP), we comprehensively investigated the diagnostic and prognostic potential of FBLN5 across multiple types. We further performed a gene set enrichment analysis (GSEA) to elucidate the biological functions associated with FBLN5 expression. Additionally, a survival analysis was conducted to assess its prognostic value, and genetic alteration, methylation, and pathway analyses were also performed. Finally, we examined the relationship between FBLN5 and immunity response, and identified potential drugs that may affect the efficacy of tumor treatment. RESULTS: The analysis of TCGA data revealed that FBLN5 RNA was differentially expressed across multiple tumor types, and in 92% of tumor types, the expression level of FBLN5 protein is lower. Genetic and epigenetic alterations-including mutations, somatic copy number alterations, and DNA methylation-were associated with its dysregulated expression. FBLN5 expression was also correlated with several key clinical features. Further, functional analyses linked FBLN5 expression to various metabolism-, metastasis-, and immune-related pathways. Elevated FBLN5 expression had a controversial effect on prognosis across multiple tumors, and influenced sensitivity to numerous therapeutic agents. Additionally, FBLN5 expression showed significant correlations with immunoregulatory molecules and biomarkers indicative of lymphocyte subpopulation infiltration. CONCLUSIONS: This study conducted a systematic analysis of FBLN5 and its regulatory network, demonstrating that FBLN5 expression is closely associated with DNA methylation and drug resistance across multiple tumor types. Further, FBLN5 was found to remodel the tumor microenvironment and cause resistance to immunotherapy.
-
Atlas of amnion development during the first trimester of human pregnancy.
The amnion is a critical extra-embryonic structure that supports foetal development, yet its ontogeny remains poorly defined. Here, using single-cell transcriptomics, we identified major cell types and subtypes in the human amnion across the first trimester of pregnancy, broadly categorized into epithelial, mesenchymal and macrophage lineages. We uncovered epithelial-mesenchymal and epithelial-immune transitions, highlighting dynamic remodelling during early pregnancy. Our results further revealed key intercellular communication pathways, including BMP4 signalling from mesenchymal to epithelial cells and TGF-β signalling from macrophages to mesenchymal cells, suggesting coordinated interactions that drive amnion morphogenesis. In addition, integrative comparisons across humans, non-human primates and in vitro stem cell-based models reveal that stem cell-based models recapitulate various stages of amnion development, emphasizing the need for careful selection of model systems to accurately recapitulate in vivo amnion formation. Collectively, our findings provide a detailed view of amnion cellular composition and interactions, advancing our understanding of its developmental role and regenerative potential.
-
N6-methyladenosine (m6A) RNA methylation regulator SNRPC is a prognostic biomarker and is correlated with immunotherapy in hepatocellular carcinoma.
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world, and due to its complex pathogenic factors, its prognosis is poor. N6-methyladenosine (m6A) RNA methylation plays an important role in the tumorigenesis, progression, and prognosis of many tumors. The m6A RNA methylation regulator small nuclear ribonucleoprotein polypeptide C (SNRPC), which encodes one of the specific protein components of the U1 small nuclear ribonucleoprotein (snRNP) particle, has been proven to be related to the prognosis of patients with HCC. However, the effect of SNRPC on the tumor microenvironment and immunotherapy in HCC remains unclear. CASE PRESENTATION: The HCC RNA-seq profiles in The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, including 421 LIHC and 440 LIRI-JP samples, respectively, were used in this study. Both the expression of SNRPC in HCC was upregulated in the TCGA and ICGC databases compared to normal tissues. Next, the expression of SNRPC was validated as a risk factor for prognosis by Kaplan-Meier analysis and employed to establish a nomogram with T pathologic stage. By gene set variation (GSVA) analysis and gene set enrichment (GSEA) analysis, we found that SNRPC was mainly related to protein metabolism and the immune process. Furthermore, the estimation of stromal and immune cells in malignant tumor tissues using expression (ESTIMATE), microenvironment cell population counter (MCP-counter), and single sample GSEA (ssGSEA) algorithms revealed that the high-SNRPC group had a lower stromal score, lower abundance of endothelial cells and fibroblasts, and lower immune infiltration. Ultimately, a tumor immune dysfunction and exclusion (TIDE) analysis revealed that patients in the low-SNRPC group may be more sensitive to immune checkpoint inhibitor therapy. CONCLUSION: SNRPC could serve as a promising prognostic and immunotherapeutic marker in HCC and might contribute to new directions and strategies for HCC treatment.
-
Transcriptomic landscape of mammalian ventral pallidum at single-cell resolution.
The ventral pallidum (VP) is critical for motivated behaviors. While contemporary work has begun to elucidate the functional diversity of VP neurons, the molecular heterogeneity underlying this functional diversity remains incompletely understood. We used single-nucleus RNA sequencing and in situ hybridization to define the transcriptional taxonomy of VP cell types in mice, macaques, and baboons. We found transcriptional conservation between all three species, within the broader neurochemical cell types. Unique dopaminoceptive and cholinergic subclusters were identified and conserved across both primate species but had no homolog in mice. This harmonized consensus VP cellular atlas will pave the way for understanding the structure and function of the VP and identified key neuropeptides, neurotransmitters, and neurotransmitter receptors that could be targeted within specific VP cell types for functional investigations.
-
Integrated single cell and unsupervised spatial transcriptomic analysis defines molecular anatomy of the human dorsolateral prefrontal cortex.
Generation of a molecular neuroanatomical map of the human prefrontal cortex reveals novel spatial domains and cell-cell interactions relevant for psychiatric disease. The molecular organization of the human neocortex has been historically studied in the context of its histological layers. However, emerging spatial transcriptomic technologies have enabled unbiased identification of transcriptionally-defined spatial domains that move beyond classic cytoarchitecture. Here we used the Visium spatial gene expression platform to generate a data-driven molecular neuroanatomical atlas across the anterior-posterior axis of the human dorsolateral prefrontal cortex (DLPFC). Integration with paired single nucleus RNA-sequencing data revealed distinct cell type compositions and cell-cell interactions across spatial domains. Using PsychENCODE and publicly available data, we map the enrichment of cell types and genes associated with neuropsychiatric disorders to discrete spatial domains. Finally, we provide resources for the scientific community to explore these integrated spatial and single cell datasets at research.libd.org/spatialDLPFC/.
-
Decrypting spatiotemporal code of human endometrial receptivity.
The mechanism underlying the establishment of human endometrial receptivity remains elusive, constituting a significant obstacle to advancing our knowledge of female infertility. Via integrating high-resolution spatiotemporal and single-cell transcriptomic profiling and in situ sequencing, we construct a spatiotemporal atlas of human endometrial receptivity at single-cell resolution. Our study depicts detailed spatial molecular topography governing the opening and closing of human endometrial receptivity. Notably, the results indicate that stromal-specific NR2F1, CEBPD and epithelial-specific SGK1, KLF5 and ELF3 are closely associated with the opening of implantation window. Furthermore, cholesterol metabolism is found to promote ciliogenesis. Remarkably, we identify stroma- and epithelium-specific factors and unravel a previously unappreciated role of FGFs-FGFR2 signaling pathway mediating stroma-epithelium crosstalk in epithelial differentiation during the onset of receptivity. This spatiotemporally resolved receptivity code provides insights into the female fertility, with potential implications for the intervention of female infertility.
-
Single-cell transcriptomics reveals immune suppression and cell states predictive of patient outcomes in rhabdomyosarcoma.
Paediatric rhabdomyosarcoma (RMS) is a soft tissue malignancy of mesenchymal origin that is thought to arise as a consequence of derailed myogenic differentiation. Despite intensive treatment regimens, the prognosis for high-risk patients remains dismal. The cellular differentiation states underlying RMS and how these relate to patient outcomes remain largely elusive. Here, we use single-cell mRNA sequencing to generate a transcriptomic atlas of RMS. Analysis of the RMS tumour niche reveals evidence of an immunosuppressive microenvironment. We also identify a putative interaction between NECTIN3 and TIGIT, specific to the more aggressive fusion-positive (FP) RMS subtype, as a potential cause of tumour-induced T-cell dysfunction. In malignant RMS cells, we define transcriptional programs reflective of normal myogenic differentiation and show that these cellular differentiation states are predictive of patient outcomes in both FP RMS and the less aggressive fusion-negative subtype. Our study reveals the potential of therapies targeting the immune microenvironment of RMS and suggests that assessing tumour differentiation states may enable a more refined risk stratification.
-
NCBP2 predicts the prognosis and the immunotherapy response of cancers: a pan-cancer analysis.
BACKGROUND: The cap-binding complex (CBC) plays a crucial role in facilitating gene expression by safeguarding mRNA from nonsense-mediated decay, promoting mRNA splicing, 3'-end processing, and facilitating nuclear export. Nevertheless, the precise biological functions and clinical implications of CBC in cancer remain ambiguous, necessitating further investigation for clarification. METHODS: The present study utilized the cBioPortal database to investigate the genetic alterations of nuclear cap binding protein subunit 2 (NCBP2) in pan-cancer. The Cancer Genome Atlas (TCGA) and online web tools were employed to analyze the correlation between NCBP2 and prognosis, genome instability, immune infiltration, immune response, cancer stemness, and chemotherapeutic efficacy in pan-cancer. Furthermore, the expression of NCBP2 was confirmed by immunohistochemistry (IHC) and functional analysis at the single-cell level was conducted using the CancerSEA database. RESULTS: NCBP2 exhibited distinct genetic alterations in pan-cancer with an increased expression in 24/32, while decreased expression in 3/32, types of cancers. IHC confirmed the aberrant expression of NCBP2 in lung squamous cell carcinoma (LUSC), pancreatic adenocarcinoma (PAAD), kidney renal papillary cell carcinoma (KIRP) and kidney renal clear cell carcinoma (KIRC). NCBP2 was correlated with overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS) in various cancers. Importantly, it was identified as a risk factor for OS, DSS and PFS in PAAD and uterine corpus endometrial carcinoma (UCEC). Gene Set Enrichment Analysis (GSEA) demonstrated that elevated NCBP2 was linked to immune and proliferation related pathways across multiple cancer types. Furthermore, a negative association between NCBP2 and stromal score, immune score, and ESTIMATE score was detected, and a positive correlation was observed between NCBP2 and diverse immune cells as well as stemness-indexes in the majority of cancer types. Drug sensitivity analysis revealed that drugs associated with NCBP2 primarily targeted DNA replication, chromatin histone methylation, ABL signaling, cell cycle, and PI3K signaling. Additionally, an examination at the single-cell level indicated that NCBP2 was positively correlated with cell cycle progression, DNA damage, DNA repair, invasion, and stemness in most cancer types, while negatively correlated with apoptosis, inflammation, and hypoxia in certain cancers. CONCLUSION: In this study, we revealed the correlation of NCBP2 with prognosis, microenvironment and stemness, indicating that NCBP2 might be a potential therapeutic target for more effective and personalized therapy strategies in pan-cancer.
-
Development and validation of a prognostic model for efferocytosis-associated genes in cervical squamous cell carcinoma.
BACKGROUND: Genes associated efferocytosis play a critical role in tumor invasion, metastasis, and clinical outcomes in several malignancies. However, their prognostic relevance in cervical squamous carcinoma (CESC) is currently unclear. METHODS: Data from the Cancer Genome Atlas (TCGA) database were used to create the TCGA-CESC cohort. Additional CESC-related datasets (GSE44001 and GSE168652) were retrieved from the Gene Expression Omnibus database. Single-cell analysis of the GSE168652 dataset was conducted to identify differentially expressed genes (DEGs), associated with efferocytosis (ER-DEGs). CESC samples from the TCGA cohort were classified into clusters, and prognosis-related DEGs (PR-DEGs) were identified by comparing these clusters. The intersection of ER-DEGs and PR-DEGs generated a subset of prognosis-efferocytosis related DEGs (PER-DEGs). Subsequently, a risk model was developed using univariate Cox regression and least absolute shrinkage and selection operator analysis. Independent prognostic factors were further analyzed using Cox regression analysis. Functional pathways were examined through gene set enrichment analysis. RESULTS: A total of 15 cell clusters were identified from the GSE168652 dataset and categorized into seven distinct cell types. Comparative analysis indicated 774 ER-DEGs between groups with high and low ERG expression levels. From these, 332 PER-DEGs were identified. A prognostic risk model was constructed based on seven characteristic genes: ITGA5, SNRPF, EGLN1, NDUFB7, NDUFA2, SRGAP3, and PCNA. Risk score and pathologic-N emerged as independent prognostic factors. These genes were found to be associated with multiple pathways implicated in the pathogenesis of CESC. CONCLUSION: Seven efferocytosis-related prognostic genes were identified as prognostic markers for CESC, providing a scientific basis for further research on their role in disease progression.
-
Identification of prognostic biomarkers for endometrioid endometrial carcinoma based on the miRNA and mRNA co-expression network regulated by estradiol.
BACKGROUND: Endometrioid Endometrial Carcinoma (EEC), an estradiol-related disease, remains a serious health threat to women because of its high incidence and trend of rejuvenation. Accumulating evidence has highlighted that microRNAs (miRNAs) and messenger RNAs (mRNAs) play important roles in various biological processes involved in the pathogenesis of EEC. This study aimed to identify the potential prognostic biomarkers associated with EEC regulated by estradiol. METHODS: RNA expression profiles of EEC were obtained from The Cancer Genome Atlas database (n = 408) and the original sequencing, which was performed on endometrial cancer Ishikawa cells treated with 250 nM estradiol (n = 3), 50 nM estradiol (n = 3) or control (n = 3). The TargetScan database was used to predict the target genes of prognosis-related differentially expressed miRNAs (DEMs). Subsequently, functional enrichment analysis and topological analysis were performed on the overlaps of target genes and differentially expressed mRNAs (DEGs). Kaplan-Meier analysis was used to predict prognosis-related target genes to identify prognostic biomarkers and cell population landscapes, and gene expression analysis was performed to locate prognosis-related DEGs based on single-cell transcriptomic sequencing data from the NCBI Sequence Read Archive database. RESULTS: Four estradiol-related DEGs were associated with prognosis, and 235 overlapping target DEGs were screened and incorporated into the functional enrichment analysis and protein-protein interaction network visualization studies. Additionally, SACS and GPR157 were identified as potential biomarkers for EEC prognosis through survival analyses. Furthermore, single-cell transcriptome data were analyzed to show changes in gene expression levels in specific cell types. CONCLUSIONS: This study demonstrates that miR-142-5p-SACS and miR-30a-5p-GPR157, which are regulated by estradiol, may hold promise as diagnostic and prognostic biomarkers and novel therapeutic targets for EEC.