Elucidating stearoyl metabolism and NCOA4-mediated ferroptosis in gastric cancer liver metastasis through multi-omics single-cell integrative mendelian analysis: advancing personalized immunotherapy strategies

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 15, 2025

The metabolism of stearoyl-GPE plays a key role in the liver metastasis gastric cancer. This investigation delves into mechanisms underlying intricate tumor microenvironment (TME) heterogeneity triggered by stearoyl cancer with (LMGC), offering novel perspectives for LMGC. Utilizing Mendelian randomization, we determined that significantly contributes to progression (GC). Following this, bulk transcriptome analyses and single-cell multiomics techniques investigate roles metabolism-related genes, particularly NCOA4, regulating LMGC TME. Our analysis highlights crucial modulating complex LMGC, impacting monocyte cells. Through sequencing spatial transcriptomics, have identified metabolic genes specific within cell population, including NCOA4. Regarding relationship between ferroptosis, metabolism, findings, it is plausible pathways intersect involved ferroptosis. Ferroptosis, characterized iron-dependent lipid peroxidation, represents regulated form death. activity Stearoyl-CoA desaturase (SCD), critical enzyme has been associated modulation composition susceptibility Furthermore, integral cellular processes related oxidative stress both which are significant factors context study enhances understanding ferroptosis promoting its regulation heterogeneity. In addition, this deeper dynamics provides basis development better interventions combat metastasis.

Language: Английский

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Integrating multi-omics and experimental techniques to decode ubiquitinated protein modifications in hepatocellular carcinoma

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 11, 2025

Background Ubiquitination, a critical post-translational modification, plays pivotal role in regulating protein stability and activity, influencing various aspects of cancer development, including metabolic reprogramming, immune evasion, tumor progression. However, the specific ubiquitination hepatocellular carcinoma (HCC), particularly relation to microenvironment (TME), remains poorly understood. This study aims systematically explore shaping TME HCC, with focus on its impact progression modulation. Methods We performed bioinformatics analysis by integrating multiple publicly available HCC datasets assess status across cell types TME, plasma cells, fibroblasts, endothelial epithelial-mesenchymal transition (EMT) cells. Ubiquitination scores were calculated categorize these types, survival data, along spatial transcriptomics, employed evaluate how different levels influence In vitro experiments, such as transwell, CCK8, wound healing assays, used further investigate key gene UBE2C phenotypes. Results Our revealed that ubiquitination-related genes are significantly upregulated tissues, high expression correlating poor prognosis patients. Pathway showed enriched processes cycle regulation, DNA repair, p53 signaling. These pathways contribute promoting proliferation, facilitating matrix remodeling, enhancing angiogenesis. Notably, UBE2C, enzyme, appears play potentially inhibiting anti-tumor responses reducing system’s ability recognize eliminate Furthermore, experimental data confirmed overexpression promotes invasion, metastasis, supporting remodeling. Conclusion reveals multifaceted regulatory roles HCC. not only supports proliferation anti-apoptotic functions within cells but also modulating activity stromal Among all genes, emerges potential prognostic biomarker therapeutic target offering new directions for precision treatment future.

Language: Английский

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Integrated single-cell RNA sequencing reveals the tumor heterogeneity and microenvironment landscape during liver metastasis in adenocarcinoma of esophagogastric junction

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

Published: Jan. 9, 2025

Adenocarcinoma of the esophagogastric junction (AEGJ) is a highly aggressive tumor that frequently metastasizes to liver. Understanding cellular and molecular mechanisms drive this process essential for developing effective therapies. We employed single-cell RNA sequencing analyze heterogeneity microenvironmental landscape in patients with AEGJ liver metastases. This approach enabled us characterize diverse cell populations involved metastatic process. Our analysis revealed significant involvement fibroblasts mural cells metastasis. identified specific fibroblast type metastasis observed distinct gene expression patterns between adenocarcinoma other stomach adenocarcinomas. study demonstrated high SFRP2 pericyte during AEGJ. The incorporation GEO, TCGA, immunofluorescence staining enhanced our study. High pericytes may influence vascular stability angiogenesis through Wnt pathway. provides novel insights into interactions underlie Targeting subtype or influencing offer new therapeutic strategies combating tumor.

Language: Английский

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Causal Association Between Microbiome and Oral-Oropharyngeal Cancer: A Mendelian Randomization Study

International Dental Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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From big data and experimental models to clinical trials: Iterative strategies in microbiome research

Cell, Journal Year: 2025, Volume and Issue: 188(5), P. 1178 - 1197

Published: March 1, 2025

Microbiome research has expanded significantly in the last two decades, yet translating findings into clinical applications remains challenging. This perspective discusses persistent issue of correlational studies microbiome and proposes an iterative method leveraging silico, vitro, ex vivo, vivo toward successful preclinical trials. The evolution methodologies, including shift from small cohort to large-scale, multi-cohort, even "meta-cohort" analyses, been facilitated by advancements sequencing technologies, providing researchers with tools examine multiple health phenotypes within a single study. integration multi-omics approaches-such as metagenomics, metatranscriptomics, metaproteomics, metabolomics-provides comprehensive understanding host-microbe interactions serves robust hypothesis generator for downstream vitro research. These hypotheses must then be rigorously tested, first proof-of-concept experiments clarify causative effects microbiota, goal deep mechanistic understanding. Only following these phases can conducted translation clinic. We highlight importance combining traditional microbiological techniques big-data approaches, underscoring necessity diverse model systems enhance translational potential

Language: Английский

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Exploring novel biomarkers and immunotherapeutic targets for biofeedback therapies to reveal the tumor-associated immune microenvironment through a multimetric analysis of kidney renal clear cell carcinoma

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 13, 2025

Kidney renal clear cell carcinoma (KIRC) constitutes the primary subtype of carcinoma, representing 75% to 80% cases and carrying a substantial cancer-specific mortality rate up 24%. Despite advancements in treatment options, KIRC displays notable resistance conventional therapies, emphasizing need for innovative targeted immunotherapeutic strategies. Chromatin regulators (CRs), pivotal proteins controlling gene expression critical biological processes, play crucial role initiation progression KIRC. This study employed multi-omics approach evaluate impact CR-associated genes on prognosis. The utilized TCGA-KIRC dataset LASSO Cox regression construct validate prognostic model that focuses influencing research investigated interactions among characteristics, clinical parameters, tumor microenvironment, immunotherapy, drug responsiveness. Experimental validation, encompassing various techniques such as culture, transient transfection, qPCR, Transwell assays, confirmed robust predictive capability BRD9 gene. analysis identified risk score CRs an independent factor determining Furthermore, introduced Nomogram integrates attributes assessment. Significantly, exhibited substantially elevated within cells, underscoring its driving cancer proliferation, invasion, migration. These findings suggest potential tailored immunotherapy targeting presents framework based approaches, seamlessly incorporating CRs. holds promise improving accuracy prognosis prediction patients, laying foundation development immunotherapies.

Language: Английский

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Innovative strategies to optimise colorectal cancer immunotherapy through molecular mechanism insights

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 9, 2024

Colorectal cancer (CRC) is a leading cause of cancer-related deaths globally. The heterogeneity the tumor microenvironment significantly influences patient prognosis, while diversity cells shapes its unique characteristics. A comprehensive analysis molecular profile crucial for identifying novel targets drug sensitivity and uncovering pathophysiological mechanisms underlying CRC.

Language: Английский

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Exploring the role of Disulfidptosis in glioma progression: insights into tumor heterogeneity and therapeutic potential through single-cell RNA sequencing

Discover Oncology, Journal Year: 2024, Volume and Issue: 15(1)

Published: Dec. 23, 2024

Gliomas, particularly glioblastoma (GBM), are the most common and aggressive primary brain tumors in adults, characterized by high malignancy frequent recurrence. Despite standard treatments, including surgery, radiotherapy, chemotherapy, prognosis for GBM remains poor, with a median survival of less than 15 months five-year rate below 10%. Tumor heterogeneity resistance to treatment create significant challenges controlling glioma progression. Therefore, there is an urgent need new therapeutic targets strategies. This study investigates role Disulfidptosis, recently discovered form programmed cell death, gliomas. Unlike apoptosis necrosis, Disulfidptosis driven abnormal accumulation intracellular disulfide bonds, leading protein misfolding cytoskeletal collapse, cancer cells metabolic dysregulation. We aim explore how respond identify potential analyzing gliomas at single-cell level using RNA sequencing (scRNA-seq). scRNA-seq data from patients were analyzed uncover differences ferroptosis-related pathways, iron metabolism lipid peroxidation. Cellular subpopulations within profiled assess their sensitivity underlying mechanisms. Survival analysis was conducted evaluate clinical relevance Disulfidptosis-related gene expression. Multiple exhibit varying sensitivities influenced properties. Dysregulated antioxidant mechanisms identified as key factors impacting sensitivity. Glioma microenvironment signaling pathways also play regulating Disulfidptosis. These findings suggest that activating may provide novel strategies overcome offers insights into progression highlights its target. By leveraging data, research uncovers tumor identifies specific populations resistant pave way personalized improve outcomes patients.

Language: Английский

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Mitochondria: a crucial factor in the progression and drug resistance of colorectal cancer

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 23, 2024

Colorectal cancer (CRC), as one of the malignant tumors with highest incidence and mortality rates worldwide in recent years, originating primarily from mucosal tissues colon or rectum, has potential to rapidly develop into invasive cancer. Its pathogenesis is complex, involving a multitude factors including genetic background, lifestyle, dietary habits. Early detection treatment are key improving survival for patients CRC. However, pervasive problem that can become severely resistant treatment, which greatly increases complexity challenge treatment. Therefore, unraveling overcoming resistance CRC focus research. Mitochondria, energy centers cell, play crucial role cellular metabolism, supply, apoptosis process. In CRC, Mitochondrial dysfunction not only impairs normal cell function but also promotes tumor resistance. deep understanding relationship between mitochondrial mechanisms development, well by it chemotherapy drugs, development targeted therapies, enhancing drug efficacy, outcomes quality life patients.

Language: Английский

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Multi-omics analysis reveals the role of the autophagy-related gene AGT in chemotherapy resistance in colorectal cancer and the therapeutic potential of its inhibitors

Discover Oncology, Journal Year: 2024, Volume and Issue: 15(1)

Published: Nov. 18, 2024

Autophagy is a crucial mechanism for maintaining cellular homeostasis and responding to environmental stress, it closely linked tumor drug resistance. Through multi-omics analysis, this study explores the expression patterns, functions, potential role of autophagy-related gene Angiotensinogen (AGT) in colorectal cancer (CRC), particularly relation chemotherapy This first compared AGT between CRC normal tissues using GTEx TCGA databases. Differences were assessed Wilcoxon Rank Sum Tests, prognostic impact was evaluated through univariate Cox survival analysis meta-analysis. Functional enrichment performed limma fgsea packages. Drug sensitivity conducted based on CTRP database, while immune infiltration CIBERSORT ESTIMATE methods. Spatial transcriptomic characteristics explored 10x Visium technology deconvolution investigate correlation levels cell content.scRNA-seq data from sourced Tumor Immune Single Cell Hub (TISCH).Functional annotation with Single-sample set (SSGSEA), pseudotime Monocle 2 mapped their developmental trajectories. The inhibitors treatment analyzed drug-target Mendelian randomization.Finally, Phenome-Wide Association Study (PheWAS) evaluate genetic associations side effects inhibitors. significantly higher associated shorter recurrence-free (RFS). signaling pathways markedly enriched high group. positively correlated resistance chemotherapeutic agents such as gemcitabine, cisplatin, paclitaxel, 5-fluorouracil. revealed that predominantly expressed malignant regions. Single-cell identified 21 distinct subpopulations across 13 major types. samples, especially fibroblast C6 subpopulation. Tumor-related C1, C5, C6, C8 subpopulations. Pseudotime these subpopulations, terminal stages.Drug-target randomization indicated negative causal relationship risk both heart failure(ORdrug = 0.950, 95% CI, 0.912–0.990; P 0.014) CRC(ORdrug 0.874, CI: 0.792–0.964; 0.007).PheWAS showed no other traits, indicating its specificity low effects. Elevated chemotherapy, inhibition may offer therapeutic avenue cancer.

Language: Английский

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