ALDOB suppresses the activity of CD8⁺ T cells in colorectal cancer via the WNT signaling pathway

Immunology and Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

Abstract The glycolytic enzyme, fructose‐1,6‐bisphosphate aldolase B (ALDOB), is recognized for its key role in shaping tthe umor immune microenvironment. However, the precise ways which it influences CD8 + T cell response colorectal cancer (CRC) are still largely unknown. This study designed to elucidate interplay between ALDOB and system CRC. We analyzed high expression of CRC tissues cells through bioinformatics, clinical samples vitro experiments, finding that promoted tumor progression. Its was negatively correlated with positively PDL1 expression. Further experiments revealed overexpression enhanced WNT signaling pathway‐related proteins (β‐catenin c‐myc), turn cells, inhibiting proliferation killing effect co‐culture systems. Our findings disclose how recruitment antitumor function, proposing as a potential target treatment

Language: Английский

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Screening of differential gene expression patterns through survival analysis for diagnosis, prognosis and therapies of clear cell renal cell carcinoma

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(9), P. e0310843 - e0310843

Published: Sept. 30, 2024

Clear cell renal carcinoma (ccRCC) is the most prevalent subtype of kidney cancer. Although there increasing evidence linking ccRCC to genetic alterations, exact molecular mechanism behind this relationship not yet completely known researchers. Though drug therapies are best choice after metastasis, unfortunately, majority patients progressively develop resistance against therapeutic drugs receiving it for almost 2 years. In case, multi-targeted different variants essential effective treatment ccRCC. To understand mechanisms development and progression, explore drugs, identify ccRCC-causing key genes (KGs). order obtain KGs, at first, we detected 133 common differentially expressed (cDEGs) between control samples based on nine (9) microarray gene-expression datasets with NCBI accession IDs GSE16441, GSE53757, GSE66270, GSE66272, GSE16449, GSE76351, GSE66271, GSE71963, GSE36895. Then, filtered these cDEGs through survival analysis independent TCGA GTEx database obtained 54 scDEGs having significant prognostic power. Next, used protein-protein interaction (PPI) network reduced set top-ranked eight KGs ( PLG , ENO2 ALDOB UMOD ALDH6A1 SLC12A3 SLC12A1 SERPINA5 ). The pan-cancer showed association subtypes cancers including gene regulatory (GRN) revealed some crucial transcriptional post-transcriptional regulators KGs. scDEGs-set enrichment significantly identified functions, biological processes, cellular components, pathways that linked results DNA methylation study indicated hypomethylation hyper-methylation which may lead immune infiltrating types (CD8+ T CD4+ cell, B neutrophil, dendritic macrophage) their in ccRCC, where positively correlated cells, but negatively other supported by literature review also. Then 10 repurposable molecules (Irinotecan, Imatinib, Telaglenastat, Olaparib, RG-4733, Sorafenib, Sitravatinib, Cabozantinib, Abemaciclib, Dovitinib.) docking KGs-mediated receptor proteins. Their ADME/T cross-validation receptors, also potent Therefore, outputs might be useful inputs/resources wet-lab researchers clinicians considering an strategy

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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Construction and validation of a chromatin regulator-related gene signature for prognostic and therapeutic significance of clear cell renal cell carcinoma

Translational Cancer Research, Journal Year: 2024, Volume and Issue: 13(1), P. 150 - 172

Published: Jan. 1, 2024

Background: Epigenetic alterations driven by chromatin regulators (CRs) are well-recognized cancer hallmarks. Growing evidence suggests that the imbalance of CRs may lead to occurrence various diseases including tumors. However, role and prognostic value in clear cell renal carcinoma (ccRCC) remain undefined. Methods: Consensus clustering analysis was used identify different subtypes. Univariate multivariate Cox regression were performed prognosis-related constructed a risk model. Transcriptome sequencing verify gene expression levels. Kaplan-Meier survival compare overall (OS) between high- low-risk groups. The area under curve (AUC) receiver operating characteristic (ROC) evaluate performance ESTIMATE algorithm single-sample set enrichment (ssGSEA) executed immune characteristics samples. Correlation assess relationship score checkpoint genes, levels infiltration drug therapeutic response. Finally, we also compared differences sensitivity low- high-risk Results: We identified three CRs-related subtypes with characteristics. A model built four can precisely predict OS patients has good stability applicability further verified internal external dataset. transcriptomic validated, an independent factor for ccRCC. Obvious microenvironment checkpoints observed group. Higher activity found Besides, associated Patients be more sensitive gemcitabine, vinblastine, paclitaxel, axitinib, sunitinib, temsirolimus. Conclusions: strongly development Targeting become new strategy signature prognosis significance ccRCC, which provides important reference clinical decision-making.

Language: Английский

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Identification of a cancer driver gene-associated lncRNA signature for prognostic prediction and immune response evaluation in clear cell renal cell carcinoma

Translational Cancer Research, Journal Year: 2024, Volume and Issue: 13(7), P. 3418 - 3436

Published: July 1, 2024

Background: Clear cell renal carcinoma (ccRCC) predominates among kidney cancer cases and is influenced by mutations in driver genes (CDGs). However, significant obstacles persist the early diagnosis treatment of ccRCC. While various genetic models offer new hopes for improving ccRCC management, relationship between CDG-related long non-coding RNAs (CDG-RlncRNAs) remains poorly understood. Therefore, this study aims to construct prognostic molecular features based on CDG-RlncRNAs predict prognosis patients, provide a strategy enhance clinical management patients. Methods: This employed Cox Least Absolute Shrinkage Selection Operator (LASSO) regression analyses comprehensively investigate association lncRNAs CDGs Leveraging The Cancer Genome Atlas (TCGA) dataset, we identified 97 prognostically developed robust model these CDG-RlncRNAs. performance was rigorously validated using TCGA dataset training International Consortium (ICGC) validation. Functional enrichment analysis elucidated biological relevance CDG-RlncRNA model, particularly tumor immunity. Experimental validation further confirmed functional role representative SNHG3 progression. Results: Our revealed that are significantly associated with prognosis, enabling patient stratification into different risk groups. Development incorporating key such as HOXA11-AS, AP002807.1, APCDD1L-DT, AC124067.2, demonstrated predictive accuracy both datasets. Importantly, distinct immune-related gene expression patterns. Notably, emerged regulator cycle, highlighting its potential therapeutic target. Conclusions: established concise signature underscored pivotal It emphasizes prediction targeted therapy, offering avenues personalized intervention

Language: Английский

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The Role of m6A Methylation in Tumor Immunity and Immune-Associated Disorder

Biomolecules, Journal Year: 2024, Volume and Issue: 14(8), P. 1042 - 1042

Published: Aug. 22, 2024

N6-methyladenosine (m6A) represents the most prevalent and significant internal modification in mRNA, with its critical role gene expression regulation cell fate determination increasingly recognized recent research. The immune system, essential for defense against infections maintaining stability through interactions other bodily systems, is significantly influenced by m6A modification. This acts as a key post-transcriptional regulator of responses, though effects on different cells vary across diseases. review delineates impact major system-related cancers—including those respiratory, digestive, endocrine, nervous, urinary reproductive, musculoskeletal system malignancies, well acute myeloid leukemia autoimmune We explore pathogenic roles RNA modifications within tumor microenvironment broader highlighting how regulators interact pathways during disease progression. Furthermore, we discuss patterns these can influence susceptibility to immunotherapy, facilitating development diagnostic prognostic models pioneering new therapeutic approaches. Overall, this emphasizes challenges prospective directions m6A-related various systemic diseases throughout body.

Language: Английский

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Integrative analysis of deoxyribonuclease 1-like 3 as a potential biomarker in renal cell carcinoma

Translational Andrology and Urology, Journal Year: 2023, Volume and Issue: 12(8), P. 1308 - 1320

Published: Aug. 1, 2023

Clear cell renal carcinoma (ccRCC), the most common subtype of (RCC), is insensitive to radiotherapy and chemotherapy after surgery. Deoxyribonuclease 1-like 3 (DNASE1L3), an endonuclease that cleaves both membrane-encapsulated single- double-stranded DNA, suppresses cycle progression, proliferation metabolism in hepatocellular cells. There currently no established link between DNASE1L3 RCC inhibition. We are gonging explored mechanism underlying relationship DNASEL1L3 RCC.RNA sequencing data for tissue peritumoral were downloaded from The Cancer Genome Atlas database analyzed. expression levels normal samples verified using Gene Expression Omnibus (GEO) database, Human Protein western blotting. role potential investigated by analysis immune-related databases wound healing, invasion, counting kit 8 immunofluorescence assays.We revealed was downregulated group compared with control [The (TCGA): 7.98 vs. 10.87, P<0.001]. Meanwhile, correlated clinical characteristics patients. Patients low had worse survival (P<0.001) larger (r=-0.32, P<0.001) heavier tumors (r=-0.17, P<0.001). overexpression inhibited (786-O: 0.135±0.014 0.322±0.027, invasion 1,479±134 832±67, P<0.05) significantly tumor immune microenvironment drug sensitivity ccRCC. Moreover, level key phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway protein P-AKT decreased cells transfected DNASE1L3.This study strongly suggest may be a promising biomarker diagnosis treatment ccRCC

Language: Английский

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An 11-GRG Predicting Model for UCEC Prognosis

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 18, 2023

Abstract Background Endometrial cancer (EC) is indeed one of the most prevalent gynecological malignancies. Further research required to gain insights into molecular pathways involved in EC tumorigenesis and develop more accurate prognostic prediction methods. Method Data from Cancer Genome Atlas( TCGA) database was used validated using two GEO datasets, specifically GSE6008 GSE17025. Various bioinformatics analyses were performed, including Least Absolute Shrinkage Selection Operator regression (lasso) regression, Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) enrichment analysis Set Variation Analysis (GSVA), gene set (GSEA), protein-protein interaction (PPI) network analysis, COX calibration curves, decision curve (DCA). These aimed explore associations functions GRGs development, as well a predictive model for prognosis assessment. Results There 11 identified significantly associated with by Lasso GSEA, PPI. The further identifies 61 miRNA molecules, 24 RBPs, 139 TFs, 21 potential drugs or compounds that might have links these key genes. made Cox model, among which PGK2 shows higher utility than other variables. Calibration DCA indicate clinical performance this 11-GRGs multivariate highest at 5 years, followed 3 years 1 year. 6 genes (GPI, HK1, NUP188, PDHA1, PDHA2, PGK2) exhibited accuracy time-dependent ROC curves. Conclusion highly enriched been provide new understanding development its treatment. Moreover, has constructed holds significant implications evaluating providing specific therapy guidance individuals EC. Among variables 11-GRG demonstrates notably usefulness, highlighting value

Language: Английский

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