Браузер не даёт сохранять данные (например, приватный режим): закладки пропадут после закрытия вкладки.
Поиск статей PubMed
Ключевые слова, автор, журнал, годы — результаты из PubMed, аннотации с переводом на русский, закладки в браузере.
Найдено: 4 944
Страница 374 из 495-
Reanalysis of single-cell data reveals macrophage subsets associated with the immunotherapy response and prognosis of patients with endometrial cancer.
Endometrial cancer (EC) is an aggressive gynecological malignancy with an increased incidence rate. The immune landscape crucially affects immunotherapy efficacy and prognosis in EC patients. Here, we characterized the distinct tumor microenvironment signatures of EC tumors by analyzing single-cell RNA sequencing data from Gene Expression Omnibus and bulk RNA sequencing data from The Cancer Genome Atlas, which were compared with normal endometrium. Three macrophage subsets were identified, and two of them showed tissue-specific distribution. One of the macrophage subsets was dominant in macrophages derived from EC and exhibited characteristic behaviors such as promoting tumor growth and metastasis. One of the other macrophage subsets was mainly found in normal endometrium and served functions related to antigen presentation. We also identified a macrophage subset that was found in both EC and normal endometrial tissue. However, the pathway and cellular cross-talk of this subset were completely different based on the respective origin, suggesting a tumor-related differentiation mechanism of macrophages. Additionally, the tumor-enriched macrophage subset was found to predict immunotherapy responses in EC. Notably, we selected six genes from macrophage subset markers that could predict the survival of EC patients, SCL8A1, TXN, ANXA5, CST3, CD74 and NANS, and constructed a prognostic signature. To verify the signature, we identified immunohistochemistry for the tumor samples of 83 EC patients based on the selected genes and further followed up with the survival of the patients. Our results provide strong evidence that the signature can effectively predict the prognosis of EC patients.
-
Thymosin α1 alleviates pulpitis by inhibiting ferroptosis of dental pulp cells.
Tooth pulpitis is a prevalent oral disorder. Understanding the underlying mechanisms of pulpitis and developing effective treatment strategies hold great significance. Ferroptosis has recently emerged as a new form of cell death, but the role of ferroptosis in pulpitis remains largely unknown. In our study, single-cell RNA sequencing (scRNA-seq) was used to identify cellular heterogeneity between 3 pulpitis tissue and 3 healthy pulp tissue, and explored ferroptosis occurrence in pulpitis tissue and inflamed dental pulp cells (DPCs). In scRNA-seq, 40 231 cells (Pulpitis: 17 814; Healthy pulp: 22 417) were captured, and visualized into 12 distinct cell clusters. Differentially expressed ferroptosis-related genes (DE-FRGs) were almost presented in each cluster in pulpitis vs healthy pulp. ROS and Fe2+ levels significantly rose, and immunohistochemistry showed low expression of GPX4 and high expression of PTGS2 in pulpitis. In LPS-stimulated DPCs, thymosin α1 increased the expression of GPX4 and FTL, and decreased expression of TNF-α, IL-1β, IL-6, and Fe2+ levels. In rat pulpitis models, both prothymosin α (PTMA, precursor of thymosin α1) gelatin sponge placed at the hole of pulp (LPS-P(gs)) and PTMA injection in pulp (LPS-P(i)) significantly reduced infiltration of inflammatory cells and expression of PTGS2, and increased the expression of GPX4. In RNA sequencing, the expression of DE-FRGs were reversed when thymosin α1 were added in LPS-stimulated DPCs. Collectively, single-cell atlas reveals cellular heterogeneity between pulpitis and healthy pulp, and ferroptosis occurrence in pulpitis. Thymosin α1 may reduce ferroptosis in DPCs to alleviate pulpitis and thus potentially has the ability to treat pulpitis.
-
Non-structural maintenance of chromosome condensin I complex subunit H knockdown suppresses malignant progression of esophageal squamous cell carcinoma via the Wnt/β-catenin signaling pathway.
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) remains a major cause of cancer-related mortality, and effective therapeutic targets are still limited. Non-structural maintenance of chromosome condensin I complex subunit H (NCAPH) has been implicated in tumorigenesis; however, its clinical relevance, functional roles, and underlying mechanisms in ESCC are not fully defined. We aimed to characterize the expression pattern, prognostic value, biological functions, and mechanistic basis of NCAPH in ESCC. METHODS: Public datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to evaluate NCAPH expression and clinical associations. Single-cell RNA sequencing (scRNA-seq) data were used to map cell-type-specific distribution of NCAPH in tumor and adjacent tissues. NCAPH was silenced in KYSE150 and KYSE510 cells using lentiviral short hairpin RNAs (shRNAs), followed by Cell Counting Kit-8 (CCK-8), colony formation, wound-healing, and Transwell migration/invasion assays. A nude mouse xenograft model was established to assess the effect of NCAPH knockdown in vivo. RNA sequencing (RNA-seq), quantitative polymerase chain reaction (qPCR), western blotting, and enzyme-linked immunosorbent assay (ELISA) were performed to explore potential mechanisms. RESULTS: NCAPH was consistently upregulated in ESCC across multiple cohorts and was associated with unfavorable clinicopathological features and poorer survival. Functional assays demonstrated that NCAPH knockdown significantly inhibited ESCC cell proliferation, migration, invasion, and clonogenic growth. In vivo, NCAPH silencing suppressed xenograft tumor growth. Mechanistically, transcriptomic profiling and molecular validation indicated attenuation of Wnt/β-catenin signaling following NCAPH depletion, accompanied by reduced β-catenin and downstream targets. CONCLUSIONS: NCAPH promotes malignant progression of ESCC, at least in part through activation of the Wnt/β-catenin pathway, and may serve as a potential biomarker and therapeutic target.
-
Single-cell and machine learning-based pyroptosis-related gene signature predicts prognosis and immunotherapy response in glioblastoma.
BACKGROUND: Glioblastoma (GBM) is the most aggressive primary malignancy of the central nervous system, characterized by profound heterogeneity and an immunosuppressive microenvironment, leading to dismal prognosis. Pyroptosis, an inflammatory form of programmed cell death, has been increasingly linked to tumor immunity and progression; however, its molecular roles and clinical implications in GBM remain insufficiently understood. METHODS: We integrated bulk transcriptome profiles from TCGA-GBM, CGGA, and GEO datasets with single-cell RNA sequencing data from GSE141383 and GSE223063. A comprehensive GBM single-cell atlas was constructed using Seurat and Harmony, and malignant epithelial cells were inferred via inferCNV. Pyroptosis activity was quantified by five complementary algorithms, while Monocle2 and Slingshot were employed for pseudotime trajectory reconstruction, and SCENIC was applied for transcription factor network analysis. Candidate prognostic genes identified from malignant epithelial subsets were further used to develop a Pyroptosis-Related Gene Signature (PRGS) through a systematic evaluation of ten machine learning algorithms and their combinations, with subsequent validation across multiple cohorts. Functional enrichment (GSVA, GSEA), tumor microenvironment estimation (ESTIMATE, ssGSEA), drug sensitivity prediction (GDSC2), and in vitro experiments were performed to characterize the biological and therapeutic relevance of PRGS, with MAP1B selected for experimental validation. RESULTS: Single-cell analyses revealed heterogeneous pyroptosis activity across GBM cell populations. Distinct ligand-receptor communications were observed between high- and low-pyroptosis groups, among which the SPP1-centered signaling axis showed pronounced remodeling, suggesting a pivotal role in tumor-immune crosstalk. Pseudotime and regulatory network analyses of malignant epithelial cells further delineated differentiation trajectories and transcriptional regulators. The PRGS, established by StepCox[both]+Ridge modeling, demonstrated robust prognostic stratification and predictive power across independent datasets. High PRGS scores were consistently associated with poorer survival outcomes, higher TIDE scores, and reduced IPS values, indicating enhanced immune evasion and attenuated immunotherapy benefit. Enrichment analyses highlighted that high PRGS tumors were linked to metabolic reprogramming and DNA repair pathways, whereas low PRGS tumors exhibited signatures of immune activation. Drug sensitivity analyses revealed distinct therapeutic vulnerabilities between subgroups. Functional assays confirmed that MAP1B promotes proliferation, migration, and invasion in GBM cells, reinforcing its oncogenic role. CONCLUSION: This study systematically elucidates the role of pyroptosis in GBM and establishes PRGS as a reliable prognostic biomarker. PRGS not only refines risk stratification and predicts immunotherapy response but also provides molecular insights into tumor metabolism and immune regulation, thereby offering potential avenues for targeted therapeutic strategies in GBM.
-
Landscape of Cell Communication in Human Dental Pulp.
The cellular atlas of the stroma is not well understood. Here, the cell populations in human dental pulp through single-cell RNA sequencing are profiled. Dental pulp stem cells, pulp cells, T cells, macrophages, endothelial cells, and glial cells are identified in human dental pulp. These cells support each other through sending growth signals. Based on the appearance of ligand-receptor pairs between two cell populations, pulp cells have the greatest communication with other cell types, while T cells have the least communication. In addition, T cells expressing TLR1, TLR2, and TLR4, and endothelial cells expressing TLR4, monitor bacterial invasion. These findings provide the census of normal dental pulp.
-
Integrated Bioinformatics Analysis Identifies NCAPG2 as an Immune-Related Prognostic Biomarker in Breast Cancer.
BACKGROUND: Non-SMC condensin II complex subunit G2 (NCAPG2) is an important molecule in regulating chromosome segregation of mitosis and acts as an oncogene and biomarker in various tumors. This study aimed to explore the role of NCAPG2 in breast cancer (BC). METHODS: The mRNA and protein expression of NCAPG2 was explored in the Gene Expression Profiling Interactive Analysis (GEPIA), Tumor Immune Estimation Resource (TIMER), Human Protein Atlas (HPA), and bc-GenExMiner databases. Survival analyses were performed using the Kaplan-Meier plotter and bc-GenExMiner databases. We used the COSMIC, CistromeDB, and cBioPortal databases to analyze the transcriptional regulation and genetic alteration. Function enrichment analyses were performed with CancerSEA and Metascape database. RESULTS: NCAPG2 expression was significantly higher in BC than normal samples. NCAPG2 expression was positively correlated with the Scarff-Bloom-Richardson (SBR) grade, HER2 status, lymph nodal status, TP53 and BRCA1/2 mutation, and Nottingham prognostic index (NPI), while negatively correlated with age, ER status, and PR status. Survival analyses indicated that overexpressed NCAPG2 was associated with the adverse prognosis of BC. Gene Set Enrichment Analysis (GSEA) and function enrichment analyses of single-cell and co-expressed genes of NCAPG2 consistently showed that NCAPG2 was involved in cell cycle, immune, DNA damage, cancer-related pathways, proliferation, and DNA repair. The result of TIMER showed that NCAPG2 was associated with infiltrating immune cells and the exhausted T cell phenotype, such as CD8+ T cells, PD-1, CTLA4, and TIM-3. CONCLUSION: We found that the mRNA and protein expression of NCAPG2 was upregulated in BC. Overexpressed NCAPG2 might act as an adverse prognosis biomarker in BRCA and had a distinct function in the cell cycle, proliferation, and immune infiltration.
-
Single-cell mapping reveals several immune subsets associated with liver metastasis of pancreatic ductal adenocarcinoma.
BACKGROUND: Identifying a metastasis-correlated immune cell composition within the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) will help to develop promising and innovative therapeutic strategies. However, the dynamics of immune cell lineages in the TME of advanced PDAC remains elusive. METHODS: Twenty-six samples from 11 patients (including 11 primary tumor tissues, 10 blood, and 5 lymph nodes) with different stages were used to develop a multiscale immune profile. High-dimensional single-cell analysis with mass cytometry was performed to search for metastasis-correlated immune changes in the microenvironment. The findings were further validated by published single-cell RNA sequencing (scRNA-seq) data and multiplex fluorescent immunohistochemistry. FINDINGS: High-dimensional single-cell profiling revealed that the three immune-relevant sites formed a distinct immune atlas. Interestingly, the PDAC microenvironment with the potential for metastatic spread to the liver was characterized by a decreased proportion of CD103+PD-1+CD39+ T cells with cytotoxic and exhausted functional status and an increased proportion of CD73+ macrophages. Analysis of scRNA-seq data of PDAC further confirmed the identified subsets and revealed strong potential interactions via various ligand-receptor pairs between the identified T subsets and the macrophages. Moreover, stratified patients with different immune compositions correlated with clinical outcomes of PDAC. CONCLUSIONS: Our study uncovered metastasis-correlated immune changes, suggesting that ecosystem-based patient classification in PDAC will facilitate the identification of candidates likely to benefit from immunotherapy. FUNDING: This work was supported by the National Key Research and Development Program of China, the Shanghai International Science and Technology Collaboration Program, the Shanghai Sailing Program, and the Key Laboratory of diagnosis and treatment of severe hepato-pancreatic diseases of Zhejiang Province.
-
Single-cell analysis revealed a diagnostic model of hepatocellular carcinoma based on cancer stem cell-related gene.
BACKGROUND: Cancer stem cells (CSCs) play a pivotal role in hepatocellular carcinoma (HCC) pathogenesis, driving tumor initiation, progression, metastasis, and therapeutic resistance. This study aimed to establish a reliable CSC-based signature for HCC through single-cell analysis. METHODS: The study integrates single-cell RNA sequencing (scRNA-seq) data with the Dynamic Data Retrieval Tree (DDRTree) algorithm to identify and characterize CSCs in HCC. A prognostic stemness-associated gene signature was constructed using the Cancer Genome Atlas-Liver hepatocellular carcinoma (TCGA-LIHC) cohort as the training set and validated across two independent HCC datasets (GSE14520-GPL571 and GSE14520-GPL3921). Genes with significant prognostic relevance to CSC biology were prioritized for signature inclusion. The efficacy of model was assessed via survival analysis (Kaplan-Meier) and predictive accuracy evaluation [time-dependent receiver operating characteristic (ROC) curves], demonstrating robust stratification of high- versus low-risk HCC patients and strong prognostic discrimination. RESULTS: A total of 17 CSC-related signatures in HCC were identified by copy number variation (CNV) pattern. Then, we constructed 4-CSCs-related gene predictive model by multivariate Cox regression. The model robustly stratified patients into high- and low-risk cohorts, with high-risk individuals exhibiting markedly reduced overall survival (OS). Kaplan-Meier analysis confirmed significant survival disparity between groups (P<0.001), while time-dependent ROC curves validated the model high predictive accuracy. This prognostic signature may guide the development of personalized therapeutic strategies for HCC. CONCLUSIONS: The prognostic model consisted of 4-CSC-related genes had a prognostic predictive value, providing a new perspective for precision immuno-oncology studies.
-
Multi-omic analysis of gallbladder cancer identifies distinct tumor microenvironments associated with disease progression.
Gallbladder carcinoma (GBC) is the most aggressive biliary tract cancer and is associated with a high mortality rate. Treatment of GBC faces therapeutic challenges owing to the elusive nature of in situ drivers within the local tumor microenvironment that drive its progression. Here, we created a single-cell atlas of 1,117,245 cells and a mutational landscape from 102 patients, which unveiled spatial-temporal characterizations of cellular constitutions, spatial interplays and molecular functions, and generalized five local ecosystems stratifying clinical outcomes. An integrated epithelial program, AI-EPI, combined with spatial transcriptome analysis, revealed the concurrent localization of a highly malignant tumor subtype (GM16) and AREG+ T cell, B cell, dendritic cell and macrophage subtypes within the pro-metastatic niche of primary adenocarcinomas. In vitro and in vivo experiments suggest that in addition to promoting metastasis, AREG facilitates CXCL5 expression in tumor cells through EGFR-pERK-EGR1 signaling, leading to increased neutrophil infiltration and impeding the effectiveness of immunotherapy. Our study provides a spatial-temporal landscape of the GBC microenvironment and sheds light on potential strategies for preventing immunotherapy resistance.
-
CKS2 Mediates Hepatocellular Carcinoma Recurrence After Hepatic Ischemia-Reperfusion Injury Related to M2 Macrophages.
PURPOSE: Hepatocellular carcinoma (HCC) recurrence remains a significant burden on global healthcare. Hepatic ischemia-reperfusion injury (HIRI) is a common complication in liver surgery and may be a contributing factor to HCC recurrence. Nevertheless, the potential mechanism underlying HIRI-induced HCC recurrence has not been fully elucidated. Herein, by combining bioinformatics approaches and basic experimental research, CKS2 was preliminarily identified as a crucial factor involved in HIRI-induced HCC recurrence potentially by modulating M2 macrophages. METHODS: Through performing Weighted Gene Co-Expression Network Analysis (WGCNA), differential gene expression analysis, and screening for genes associated with disease-free survival (DFS) on large-scale genomics projects including The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), the pivotal role of CKS2 in HIRI-induced HCC recurrence was determined. The clinical significance, single-cell analysis, immune cell infiltration correlation, functional enrichment, mutation landscape, and drug sensitivity of CKS2 in HCC were further characterized. Finally, CKS2 expression and function were validated through experimental techniques such as flow cytometry, immunohistochemistry, Western blot assay and quantitative real-time PCR (qRT-PCR). RESULTS: The expression of CKS2 was significantly upregulated in HIRI and HCC tissues and was closely associated with adverse clinical outcomes in HCC patients. There was a positive correlation between CKS2 expression and tumor stemness characteristics. Additionally, high CKS2 expression was strongly linked to M2 macrophage infiltration in HCC tissues. And drug sensitivity analysis indicated that HCC patients with high CKS2 expression were prone to develop drug resistance, complicating clinical anti-tumor treatment. Ultimately, the expression pattern of CKS2 and its correlation with M2 macrophages in HCC were confirmed through experimental validation. CONCLUSION: CKS2 was identified as a key factor in HIRI-induced HCC recurrence and was critically associated with M2 macrophage infiltration abundance, providing novel insights and a direction for future research.