Single-cell and bulk RNA sequencing analysis reveals CENPA as a potential biomarker and therapeutic target in cancers

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(1), P. e0314745 - e0314745

Published: Jan. 16, 2025

Cancer remains one of the most significant public health challenges worldwide. A widely recognized hallmark cancer is ability to sustain proliferative signaling, which closely tied various cell cycle processes. Centromere Protein (CENPA), a variant standard histone H3, crucial for selective chromosome segregation during cycle. Despite its importance, comprehensive pan-cancer bioinformatic analysis CENPA has not yet been conducted. Data on genomes, transcriptomes, and clinical information were retrieved from publicly accessible databases. We analyzed CENPA's genetic alterations, mRNA expression, functional enrichment, association with stemness, mutations, expression across populations cellular locations, link cycle, impact survival, relationship immune microenvironment. Additionally, prognostic model glioma patients was developed demonstrate potential as biomarker. Furthermore, drugs targeting in cells identified predicted using drug sensitivity correlations protein-ligand docking. exhibited low levels gene mutation cancers. It found be overexpressed nearly all types TCGA, relative normal controls, predominantly located nucleus malignant cells. showed strong particularly biomarker G2 phase. also emerged valuable diagnostic multiple types. In glioma, demonstrated reliable when used alongside other factors. linked Drugs such CD-437, 3-Cl-AHPC, Trametinib, BI-2536, GSK461364 target serves cancers, offering both value.

Language: Английский

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ADME gene-driven prognostic model for bladder cancer: a breakthrough in predicting survival and personalized treatment

Hereditas, Journal Year: 2025, Volume and Issue: 162(1)

Published: March 19, 2025

Abstract Background Genes that participate in the absorption, distribution, metabolism, excretion (ADME) processes occupy a central role pharmacokinetics. Meanwhile, variability clinical outcomes and responses to treatment is notable bladder cancer (BLCA). Methods Our study utilized expansive datasets from TCGA GEO explore prognostic factors cancer. Utilizing both univariate Cox regression lasso techniques, we identified ADME genes critical for patient outcomes. our study, model assessing risk was constructed. The evaluation of this model's predictive precision conducted using Kaplan–Meier survival curves assessments based on ROC curves. Furthermore, devised nomogram, offering straightforward visualization crucial indicators. To potential mediating differences between high low groups, performed comprehensive analyses including Gene Ontology (GO) Kyoto Encyclopedia Genomes (KEGG)-based enrichment analyses, immune infiltration variations, somatic mutation landscapes, pharmacological sensitivity response assessment etc. Immediately following this, selected core PPI network explored as well modulation, pathway activation. And differential expression verified by immunohistochemistry qRT-PCR. Finally pan-cancer biomarkers. Results efforts culminated establishment validated 17-gene ADME-centered prediction model, displaying remarkable accuracy BLCA prognosis. Through separate cox importance model’s score forecasting substantiated. novel nomogram incorporating variables alongside introduced. Comprehensive studies established strong correlation several key indicators: patterns cell infiltration, reactions immunotherapy, landscape profiles drug sensitivity. We screened gene CYP2C8, its tumor bioregulation upregulated found it can serve reliable biomarker pan-cancer. Conclusion formulated research stands formidable instrument prognosis, while also providing insights into disease's progression mechanisms guiding decision-making strategies.

Language: Английский

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Development and experimental validation of dephosphorylation-related biomarkers to assess prognosis and immunotherapeutic response in gliomas

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 3, 2025

Gliomas are common aggressive brain tumors with poor prognosis. Dephosphorylation-related biomarkers in a void gliomas. This study aims to construct validated prognostic risk model for dephosphorylation, which will provide new directions clinical treatment, assessment, and temozolomide (TMZ) resistance glioma patients. Screening dephosphorylation-related genes (DRGs) transcriptome expression data from The Cancer Genome Atlas (TCGA), Molecular signatures database (MSigDB) constructing scoring models. Kaplan-Meier (K-M), nomogram ROC curve were used assess the predictive efficacy of model. Gene set enrichment analysis (GSEA), immune cell infiltration, immunotherapy response chemotherapeutic drug sensitivity performed this study. correlation between drugs half maximal inhibitory concentration (IC50) values 12 DRGs was analyzed. Cell division cycle 25A (CDC25A) TMZ screened verified by experiments. Quantitative Real-Time PCR (qRT-PCR) detection mRNA human normal glial cells two lines. Transfection techniques overexpressed knocked down CDC25A. qRT-PCR Western Blot (WB) detect protein levels Subsequently, verify effect CDC25A on cells. established able accurately predict prognosis Besides, there significant differences GSEA, immunotherapeutic patients high low groups. results CCK8 experiments showed that overexpression increased susceptibility U251 LN229 TMZ, knockdown attenuated TMZ.

Language: Английский

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SCN3B is an Anti-breast Cancer Molecule with Migration Inhibition Effect

Biochemical Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

Language: Английский

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Fatty acid metabolism related gene MECR contributes to the progression of prostate cancer

Cancer Cell International, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 19, 2025

Prostate cancer (PCa) is the most common urological malignancy and second only to lung in incidence among men. Its prognosis varies widely due its heterogeneity. Research indicates that fatty acid metabolism may play a role tumor development. The gene expression profiles of PCa cell lines (GSE6919) GEO database were analyzed identify differentially expressed genes their significance relation progression-free interval. R package was employed assess overall survival clinicopathological features. study investigated effects mutations methylation on correlation with immune infiltration microenvironment, utilizing cBioPortal UALCAN resources. TIMER used TCGA project compare MECR tumours adjacent normal tissue for different or specific tumour subtypes. Furthermore, we examined impact hub progression through RT qPCR, immunohistochemistry, cellular assays. gene, which plays metabolism, has been implicated development PCa. levels are significantly associated clinical features, outcomes, Comprehensive analyses further underscore involvement prostate cancer. Additionally, closely microenvironment vitro vivo data indicated proliferation, migration, invasion. significant potential research application assessment regulation microenvironment.

Language: Английский

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PAR2 Serves an Indispensable Role in Controlling PAR4 Oncogenicity: The β-Catenin–p53 Axis

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2780 - 2780

Published: March 19, 2025

Although the role of G-protein-coupled receptors (GPCRs) in cancer is acknowledged, GPCR-based therapy rare. Mammalian protease-activated (PARs), a sub-group GPCRs, comprise four family members, termed PAR1–4. Here, we demonstrate that PAR2 dominant over PAR4 oncogene cancer. We performed knockdown Par2/f2rl1 and expressed C-terminally truncated (TrPAR2), incapable inducing signaling, to assess impact on oncogenic function by β-catenin stabilization assessment, immunoprecipitation, xenograft tumor generation Nude/Nude mice. act together promote generation. Knockdown Par2 TrPAR2 inhibited PAR4-induced levels, nuclear dishevelled 1(DVL1), TOPflash reporter activity. Likewise, invasion migration were when was knocked down or presence TrPAR2. PAR cyclic (4-4) [Pc(4-4)], PAR-based compound directed toward pleckstrin homology (PH)-binding site, effectively Pc(4-4) inhibition mediated via increase p53 level up-regulation p21 as caspase-3 well. Overall, showed absence pro-tumor functions are significantly inhibited. inhibits acting modification wt p53, thus offering powerful drug measure for fighting

Language: Английский

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MEX3A promotes cell proliferation by regulating the RORA/β-catenin pathway in hepatocellular carcinoma

World Journal of Gastrointestinal Oncology, Journal Year: 2025, Volume and Issue: 17(4)

Published: March 24, 2025

MEX3A is a member of the human homologous gene MEX-3 family. It has been shown to promote cell proliferation and migration in various cancers, indicating its potential clinical significance. However, role hepatocellular carcinoma (HCC) remains largely unexplored, with limited reports available literature. To investigate expression significance HCC explore tumor progression. We analyzed mRNA adjacent tissues using data from The Cancer Genome Atlas (TCGA). correlation between overall survival (OS) was evaluated. Immunohistochemistry performed on surgical specimens validate association parameters, including hepatitis B virus (HBV) positivity, differentiation size. Additionally, knockdown lines were constructed biological functions MEX3A. Cell assessed counting kit-8 clone formation assays, while cycle progression by flow cytometry. effects Wnt/β-catenin signaling pathway examined western blotting immunofluorescence. evaluated scratch Transwell assays. Finally, transcription factor RORA mediating explored silencing analyzing impact protein expression. TCGA analysis revealed that significantly higher compared tissues. Higher associated poorer OS. These findings validated specimens. confirmed elevated showed positive correlations Ki-67 vimentin levels. closely related HBV Mechanistic studies demonstrated inhibited progression, as reduced β-catenin, c-Myc cyclin D1. nuclear entry thereby suppressing activation downstream oncogenic pathways. depletion migratory ability cells, likely through downregulation epithelial-mesenchymal transition pathway. Transcription identified mediator effects. Silencing antagonized promotes regulating RORA/β-catenin Our suggest could serve prognostic marker therapeutic target for HCC.

Language: Английский

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Discovery of a DNA repair-associated radiosensitivity index for predicting radiotherapy efficacy in breast cancer

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: March 25, 2025

Purpose Radiotherapy is a cornerstone of breast cancer (BRCA) treatment. Accurately predicting tumor radiosensitivity critical for optimizing therapeutic outcomes and personalizing treatment strategies. DNA repair pathways are key determinants radiotherapy response. Thus, we aimed to develop novel repair-related model identify potential targets enhancing efficacy. Methods A retrospective study was conducted using data from 942 BRCA patients TCGA database. model, comprising index, developed LASSO regression analysis. Patients were stratified into radiosensitive (RS) radioresistant (RR) groups based on their index (RSI). Associations between the RSI, clinicopathological parameters, PD-L1 status analyzed. The CIBERSORT ESTIMATE algorithms employed characterize immune landscape microenvironment. Tumor Immune Dysfunction Exclusion (TIDE) algorithm pRRophetic platform used predict responses. Key genes identified in further validated vitro qRT-PCR experiments. Results We successfully constructed incorporating 10 genes. RS group exhibited significantly better prognosis compared RR group, but this benefit limited those receiving radiotherapy. This survival associated with signature absent who did not receive displayed distinct molecular profile characterized by enrichment TGF-β signaling protein secretion pathways, potentially contributing enhanced radiosensitivity. Furthermore, increased infiltration cells. Notably, RS-PD-L1-high subgroup demonstrated most favorable highest cell infiltration, highlighting responsiveness immunotherapy. In addition, heightened sensitivity CDK HER2 inhibitors. Conversely, resistance DNA-damaging drugs. These findings supported experiments MCF-7 MCF-7/IR lines, confirming differential expression Conclusion conclusion, established cancer. Our reveals strong association radiosensitivity, antitumor immunity, immunotherapy benefit, particularly within subgroup.

Language: Английский

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Identification of M1 macrophage infiltration-related genes for immunotherapy in Her2-positive breast cancer based on bioinformatics analysis and machine learning

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Over the past several decades, there has been a significant increase in number of breast cancer patients. Among four subtypes cancer, Her2-positive is one most aggressive cancers. In this study, we screened differentially expressed genes from The Cancer Genome Atlas-Breast database and analyzed relationship between immune cell infiltration using weighted gene co-expression network analysis. By constructing module − trait relationships heatmap, red module, which had highest correlation value with M1 macrophages, was selected. Twenty hub were selected based on protein–protein interaction network. Then, overlapping macrophage infiltration-related (M1 MIRGs), namely CCDC69, PPP1R16B, IL21R, FOXP3, obtained five machine-learning algorithms. Subsequently, nomogram models constructed to predict incidence outer datasets receiver operating characteristic curve analysis used validate accuracy MIRGs models. average area under for higher than 0.75 both training testing sets. After that, survival showed that expression IL21R associated overall CCDC69 PPP1R16B could lead more benefits FOXP3 immunotherapy. Lastly, conducted immunohistochemistry staining aforementioned results. conclusion, found may be helpful diagnosis, prognosis, immunotherapy cancer.

Language: Английский

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EFTUD2 is a promising diagnostic and prognostic indicator involved in the tumor immune microenvironment and glycolysis of lung adenocarcinoma

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: April 1, 2025

Elongation Factor Tu GTP Binding Domain Containing 2 (EFTUD2), a conserved spliceosomal GTPase, is involved in craniofacial development and various cancers, but its role lung adenocarcinoma (LUAD) remains unclear. EFTUD2 expression LUAD tissues was analyzed using data from TCGA GEO, validated by immunohistochemistry, RT-qPCR, Western blotting. The relationship between clinical features examined Fisher's exact test. Diagnostic prognostic analyses were performed R. Hub genes related to identified through topological algorithms, immune infiltration assessed CIBERSORT. cGAS-STING pathway m6A modification also the cohort. Functional assays conducted assess EFTUD2's impact on cell proliferation, cycle, invasion, metastasis, while glycolytic enzyme levels measured upregulated cells, correlating with N classification, visceral pleural intravascular tumor embolism, cytokeratin-19 fragment antigen 21-1. Sixteen EFTUD2-related hub identified. Higher linked altered infiltration, increased TumorPurity scores decreased StromalScore, ImmuneScore, ESTIMATEScore values. Gene enrichment highlighted involvement adhesion, response. strongly associated modification. knockdown inhibited migration, tumorigenicity, causing G0/G1 phase cycle arrest, expression. These findings may suggest that positively regulates progression of modulates activity making it valuable for treatment prognosis. potential diagnostic marker LUAD, microenvironment, pathway, modification, glycolysis.

Language: Английский

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