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 391 of 495-
Illustrating the biological functions and diagnostic value of transmembrane protein family members in glioma.
BACKGROUND: It is well-established that patients with glioma have a poor prognosis. Although the past few decades have witnessed unprecedented medical advances, the 5-year survival remains dismally low. OBJECTIVE: This study aims to investigate the role of transmembrane protein-related genes in the development and prognosis of glioma and provide new insights into the pathogenesis of the disease. METHODS: The datasets of glioma patients, including RNA sequencing data and relative clinical information, were obtained from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA) and Gene Expression Omnibus (GEO) databases. Prognostic transmembrane protein-related genes were identified by univariate Cox analysis. New disease subtypes were recognized based on the consensus clustering method, and their biological uniqueness was verified via various algorithms. The prognosis signature was constructed using the LASSO-Cox regression model, and its predictive power was validated in external datasets by receiver operating characteristic (ROC) curve analysis. An independent prognostic analysis was conducted to evaluate whether the signature could be considered a prognostic factor independent of other variables. A nomogram was constructed in conjunction with traditional clinical variables. The concordance index (C-index) and Decision Curve Analysis (DCA) were used to assess the net clinical benefit of the signature over traditional clinical variables. Seven different softwares were used to compare the differences in immune infiltration between the high- and low-risk groups to explore potential mechanisms of glioma development and prognosis. Hub genes were found using the random forest method, and their expression was based on multiple single-cell datasets. RESULTS: Four molecular subtypes were identified, among which the C1 group had the worst prognosis. Principal Component Analysis (PCA) results and heatmaps indicated that prognosis-related transmembrane protein genes exhibited differential expression in all four groups. Besides, the microenvironment of the four groups exhibited significant heterogeneity. The 6 gene-based signatures could predict the 1-, 2-, and 3-year overall survival (OS) of glioma patients. The signature could be used as an independent prognosis factor of glioma OS and was superior to traditional clinical variables. More immune cells were infiltrated in the high-risk group, suggesting immune escape. According to our signature, many genes were associated with the content of immune cells, which revealed that transmembrane protein-related genes might influence the development and prognosis of glioma by regulating the immune microenvironment. TMEM158 was identified as the most important gene using the random forest method. The single-cell datasets consistently showed that TMEM158 was expressed in multiple malignant cells. CONCLUSION: The expression of transmembrane protein-related genes is closely related to the immune status and prognosis of glioma patients by regulating tumor progression in various ways. The interaction between transmembrane protein-related genes and immunity during glioma development lays the groundwork for future studies on the molecular mechanism and targeted therapy of glioma.
-
Comprehensive characterization of NK cell-related genes in cutaneous melanoma identified a novel prognostic signature for predicting the prognosis, immunotherapy, and chemotherapy efficacy.
BACKGROUND: Natural killer (NK) cells, as key effectors of the innate immune system, play a crucial role in cancer prognosis and immunotherapy. This study aimed to develop a predictive model based on NK cell-associated immune genes (NKIGs) for patients with cutaneous melanoma (CM) and to assess its utility in predicting prognosis and guiding personalized treatment. METHODS: RNA-sequencing data and clinical information of CM patients were retrieved from The Cancer Genome Atlas (TCGA) database, while expression profiles from normal skin specimens were obtained from the Genotype-Tissue Expression (GTEx) database. Single-cell transcriptomes from CM were analyzed in conjunction with immune genes to identify NKIGs. These genes were then utilized to construct a prognostic model using univariate Cox regression and LASSO-Cox analysis. The model's accuracy and efficacy were evaluated through various statistical methods. Immunological characteristics, as well as the effectiveness of immunotherapy and chemotherapy in groups defined by the NKIGs signature, were explored. Additionally, the expression levels of NKIGs were validated via RT-qPCR in vitro experiments. RESULTS: The overall survival (OS) of patients in the low-risk group, as determined by the NKIGs signature, was significantly better than the high-risk group. The low-risk group also showed higher immune cell infiltration, particularly of CD8 T cells and activated CD4 memory T cells. CONCLUSIONS: This study has established a novel NKIGs signature with significant potential for predicting prognosis and guiding personalized therapeutic approaches in CM patients.
-
Carboxypeptidase Q(CPQ) promotes glioma progression by inducing M2 macrophage polarization and immunosuppression.
BACKGROUND: The tumor microenvironment (TME) is immunosuppressive due to the high presence of tumor-associated macrophages (TAMs). Among the different macrophage phenotypes, M2 macrophages, which are typically associated with tissue repair and immune suppression, are often the predominant form within the TME. This environment is essential for the growth and advancement of glioma. In this study, we explored whether Carboxypeptidase Q (CPQ) plays a crucial role in immune regulation of glioma by driving polarization and recruitment of M2 macrophages. METHODS: Molecular and clinical data were derived from The Cancer Genome Altas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were utilized to predict the potential biological functions of CPQ. Single-cell analysis was utilized to identify the specific cell types expressing CPQ. The GSVA algorithm was employed to calculate the activity of immune suppression signaling pathways, while the CIBERSORT algorithm was used to quantify the infiltration of immune cells. The GSEA algorithm was utilized to analyze signal pathways between CPQ high- and low-expressing groups. Human glioma specimens were collected and CPQ expression was evaluated using immunofluorescence analysis. RESULTS: CPQ was linked to immune suppression in glioma. Elevated expression of CPQ was correlated with the increased expression of immunosuppressive checkpoints, such as PD-1, TIM-3, and CTLA-4. CPQ served as an effective gene for M2 macrophage polarization and recruitment. Furthermore, it could increase radiation resistance and operate as an independent marker of poor prognosis for glioma. CONCLUSION: CPQ was implicated in immunosuppressive activities, and its elevated expression was associated with increased radiation resistance. Furthermore, CPQ served as an independent adverse prognostic biomarker for patients with glioma.
-
Decoding the spatial chromatin organization and dynamic epigenetic landscapes of macrophage cells during differentiation and immune activation.
Immunocytes dynamically reprogram their gene expression profiles during differentiation and immunoresponse. However, the underlying mechanism remains elusive. Here, we develop a single-cell Hi-C method and systematically delineate the 3D genome and dynamic epigenetic atlas of macrophages during these processes. We propose "degree of disorder" to measure genome organizational patterns inside topologically-associated domains, which is correlated with the chromatin epigenetic states, gene expression, and chromatin structure variability in individual cells. Furthermore, we identify that NF-κB initiates systematic chromatin conformation reorganization upon Mycobacterium tuberculosis infection. The integrated Hi-C, eQTL, and GWAS analysis depicts the atlas of the long-range target genes of mycobacterial disease susceptible loci. Among these, the SNP rs1873613 is located in the anchor of a dynamic chromatin loop with LRRK2, whose inhibitor AdoCbl could be an anti-tuberculosis drug candidate. Our study provides comprehensive resources for the 3D genome structure of immunocytes and sheds insights into the order of genome organization and the coordinated gene transcription during immunoresponse.
-
CCNA2 orchestrates the PI3K/AKT signaling axis to propel prostate cancer metastasis.
BACKGROUND: Prostate cancer (PCa) remains one of the most common malignancies in men, posing a persistent global burden in terms of both public health and socioeconomic costs. Although early detection is essential for improving patient outcomes, existing clinical tools, including prostate-specific antigen (PSA) screening, digital rectal examination, and transrectal ultrasound-guided biopsy, are hampered by suboptimal specificity and positive predictive value, resulting in frequent overdiagnosis and overtreatment of indolent lesions while missing a subset of aggressive tumors at an early stage. In this context, the rapid advancement of high-throughput omics technologies, coupled with sophisticated machine learning (ML) algorithms, provides a powerful computational framework to dissect high-dimensional genomic data, uncover latent gene expression signatures, and identify candidate biomarkers with superior discriminative performance over conventional clinicopathological parameters. Therefore, in this study, we sought to screen for crucial ML-based biomarkers associated with PCa, with a particular focus on systematically assessing the diagnostic and prognostic value of CCNA2. Leveraging large-scale transcriptomic cohorts from public repositories, we employed an ensemble of ML approaches to prioritize candidate genes and subsequently evaluated the diagnostic performance of CCNA2 through receiver operating characteristic curve analysis, as well as its prognostic utility via Kaplan-Meier survival estimation and multivariate Cox proportional hazards modeling. Our findings are anticipated to elucidate the molecular landscape of PCa and offer a promising biomarker candidate for early detection and risk stratification. METHODS: This study integrated single-cell RNA sequencing, bulk transcriptomic data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) repositories, immunofluorescence, and multiple ML algorithms with in vitro functional assays to evaluate CCNA2 expression, clinical relevance, and biological behavior in PCa. RESULTS: CCNA2 was linked to metastasis and poor prognosis. High CCNA2 expression significantly correlated with adverse survival outcomes, and knockdown of CCNA2 suppressed proliferation, migration, and invasion in PCa cell lines. Mechanistically, CCNA2 modulated the PI3K/AKT signaling pathway. An ML-based diagnostic model incorporating CCNA2 demonstrated high predictive accuracy across multiple validation cohorts. CONCLUSIONS: CCNA2 serves as a promising prognostic biomarker and therapeutic target in prostate adenocarcinoma, driving tumor progression potentially via the PI3K/AKT axis.
-
Comprehensive pan-cancer analysis of YBX family reveals YBX2 as a potential biomarker in liver cancer.
BACKGROUND: The Y-box-binding proteins (YBX) act as a multifunctional role in tumor progression, metastasis, drug resistance by regulating the transcription and translation process. Nevertheless, their functions in a pan-cancer setting remain unclear. METHODS: This study examined the clinical features expression, prognostic value, mutations, along with methylation patterns of three genes from the YBX family (YBX1, YBX2, and YBX3) in 28 different types of cancer. Data used for analysis were obtained from Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. A novel YBXs score was created using the ssGSEA algorithm for the single sample gene set enrichment analysis. Additionally, we explored the YBXs score's association with the tumor microenvironment (TME), response to various treatments, and drug resistance. RESULTS: Our analysis revealed that YBX family genes contribute to tumor progression and are indicative of prognosis in diverse cancer types. We determined that the YBXs score correlates significantly with numerous malignant pathways in pan-cancer. Moreover, this score is also linked with multiple immune-related characteristics. The YBXs score proved to be an effective predictor for the efficacy of a range of treatments in various cancers, particularly immunotherapy. To summarize, the involvement of YBX family genes is vital in pan-cancer and exhibits a significant association with TME. An elevated YBXs score indicates an immune-activated TME and responsiveness to diverse therapies, highlighting its potential as a biomarker in individuals with tumors. Finally, experimental validations were conducted to explore that YBX2 might be a potential biomarker in liver cancer. CONCLUSION: The creation of YBXs score in our study offered new insights into further studies. Besides, YBX2 was found as a potential therapeutic target, significantly contributing to the improvement of HCC diagnosis and treatment strategies.
-
SREBP2/Rab11s/GLUT1/6 network regulates proliferation and migration of glioblastoma.
Cholesterol serves a vital role in the occurrence and development of glioblastoma multiforme (GBM). Furthermore, cholesterol synthesis is regulated by sterol regulatory element-binding protein 2 (SREBP2), and certain glucose transporters (GLUTs) and Ras-related protein Rab11 (Rab11) small GTPase family members (Rab11s) may contribute to the process. The Cancer Genome Atlas was used to analyze the relationship between prognosis and GLUT gene expressions. To investigate the regulatory effect of Rab11s and SREBP2 on GLUTs during tumor progression, single cell RNA sequencing (scRNA-seq), western blotting and reverse transcription-quantitative PCR were performed on glioma tissues and the T98G GBM cell line. Cell viability and migration were assessed by performing MTT and wound healing assays, respectively. Moreover, the dual-luciferase reporter gene assay was conducted to predict the sterol regulatory elements in the promoter regions of the target genes. The results demonstrated that high SREBP2, GLUT1 and GLUT6 expression was associated with poor survival of patients with GBM. ScRNA-seq distinguished glioblastoma cells by EGFR and indicated the related lipid metabolism signaling pathways. Moreover, the results indicated that GLUT1 and GLUT6 were regulated by SREBP2 and Rab11s. Rab11s and SREBP2 also contributed to T98G cell viability and migration. Additionally, the results indicated that Rab11s, GLUT1 and GLUT6 were transcriptionally regulated by SREBP2. Therefore, the present study suggested that the SREBP2/Rab11/GLUT network promoted T98G cell growth, thus, identifying potential therapeutic targets for GBM.
-
A Single-Cell Atlas Revealed Altered B Cells and Neutrophils Immune Signatures and Inflammatory Responses in SFTSV Infection.
Severe fever with thrombocytopenia syndrome virus (SFTSV) presents an emerging public threat due to its high mortality rate and ever-expanding geographic distribution. However, characterization of SFTSV infection pathogenesis and immunological impact at single-cell level remains underexplored. Here, we employ single-cell transcriptome-wide sequencing in peripheral blood mononuclear cells (PBMCs) from hospitalized SFTSV-infected patients to map the immune landscape across acute and convalescent stages of infection. The results reveal significant alterations in immune cell compositions, along with profound disruption in intercellular crosstalk. B cells and neutrophils appear to be the primary target for SFTSV infection besides monocytes, as evidenced by heightened virus-related pathways in these two cell types during the acute phase. In addition, SFTSV infection induces a substantial inflammatory response, which were prominently reflected in monocytes and neutrophils. These data illustrate the complex immune remodeling and inflammatory cascades triggered by SFTSV, with a particular focus on its effects on B cells and neutrophils, bringing novel insights into future therapeutic developments.
-
Atlas of human dental pulp cells at multiple spatial and temporal levels based on single-cell sequencing analysis.
The dental pulp plays a crucial role in the long-term maintenance of tooth function. The progress of endodontic treatment and pulp tissue regeneration engineering has made pulp-regeneration therapy promising in clinical practice. However, the mechanisms of pulp regeneration and the role of dental stem cells in development and regeneration have not been fully elucidated. Bridging the gaps between clinical operation and basic research is urgently needed. With the application of single-cell sequencing technology in dental research, the landscapes of human dental pulp cells have begun being outlined. However, the specific cellular heterogeneity of dental pulp cells, especially that of dental stem cells, at different spatial and temporal levels, is still unclear. In this study, we used single-cell RNA sequencing analysis of pulp samples at four different developmental stages and combined the findings with immunohistochemical staining to explore the development of dental pulp and stem cells. The results revealed temporal changes in the proportion of pulp cells during development. For example, mononuclear phagocytes accounted for a higher proportion in early samples. Odontoblasts identified by DMP1 had a higher expression of ion channel-related and neurodevelopment-related genes. Subpopulations were identified in fibroblasts, odontoblasts, and mesenchymal stem cells. We identified a subclass of odontoblasts that expresses DGKI and RRBP1 present in early developmental samples. A population of earlier mesenchymal stem cells expressed the SEPTIN gene, which may have greater proliferative and differentiation potential. Furthermore, dental pulp stem cells can differentiate into two directions: mineralization and myogenesis. In summary, the specific cellular heterogeneity of dental pulp cells was revealed at different spatial and temporal levels. These findings may shed light on the mechanism of tooth development. The gene expression profile of developing pulp cells may help to select cells for regenerative engineering and improve the success of dental pulp regeneration.
-
Integrated transcriptomic profiling combined with in vitro validation reveals the involvement of TMEM140 in the link between periodontitis and brain aging.
OBJECTIVE: Periodontitis (PD) is a prevalent chronic inflammatory disorder in adults, and moderate-to-severe PD (Stage II-III/IV) may accelerate brain aging and neurodegenerative changes via the peripheral-central immune-neural axis, although the molecular connections and mechanisms of interaction have yet to be fully elucidated. This study sought to identify senescence-associated molecules potentially shared by PD and Alzheimer's disease (AD) using integrated transcriptomic analysis, machine learning, and in vitro RNA interference assays, and to further assess the role of TMEM140 in linking PD to brain aging. METHODS: Transcriptomic datasets related to PD and AD were retrieved from the GEO database, and differential gene expression analysis was performed following batch effect correction; shared aging-associated genes were subsequently identified by combining weighted gene co-expression network analysis (WGCNA) with aging gene databases (HAGR and aging Atlas). Four machine learning algorithms, namely random forest (RF), support vector machine (SVM), generalized linear model (GLM), and extreme gradient boosting (XGB), were further applied to identify key genes, and their diagnostic value was assessed using receiver operating characteristic (ROC) analysis and nomogram models. DSigDB was used to predict candidate small-molecule compounds. In the in vitro experiments, a Porphyromonas gingivalis lipopolysaccharide (PG-LPS)-induced inflammatory model in human gingival fibroblasts (HGFs) and an Aβ1-42 and D-galactose-induced senescence model in SH-SY5Y neuron-like cells were established; TMEM140 in SH-SY5Y cells was then silenced using small interfering RNA (siRNA), and the neuron-like cells were treated with the same batch of standardized conditioned medium (CM; prepared from the supernatant of PG-LPS-treated HGFs) to observe changes in cellular responses to inflammatory stimulation after TMEM140 downregulation. RESULTS: Seven aging-related genes common to PD and AD were identified, and comprehensive analysis using multiple algorithms selected TMEM140, TIMP1, and ALDH2 as key genes. Notably, TMEM140 was upregulated in PD and downregulated in AD, showed significant correlations with plasma cell and γδ T-cell infiltration, and single-cell analysis further revealed its cell type-specific expression in distinct brain cell subsets. In vitro experiments demonstrated that PG-LPS treatment markedly increased TMEM140 expression in HGFs, whereas treatment with Aβ1-42 and D-galactose reduced TMEM140 expression in neuron-like cells. When exposed to the same batch of conditioned medium, neuron-like cells with TMEM140 knockdown displayed more evident injury and senescence-related phenotypes, including reduced cell viability, increased reactive oxygen species (ROS) production, a higher percentage of senescence-associated β-galactosidase (SA-β-Gal)-positive cells, and marked upregulation of IL-1β, IL-6, TNF-α, p16, p21, RELA, NFKBIA, and TP53, indicating that reduced TMEM140 expression may contribute to enhanced susceptibility of neuron-like cells to inflammatory stress. CONCLUSION: Through integrated transcriptomic analysis together with in vitro experimental validation, this study indicates that TMEM140 may be a candidate bridge molecule connecting PD and AD comorbidity. TMEM140 may participate in shaping the peripheral-central immunosenescence network and contribute to the cross-system transmission of inflammatory signaling.