Exploring the role of Disulfidptosis in glioma progression: insights into tumor heterogeneity and therapeutic potential through single-cell RNA sequencing DOI Creative Commons
Xiaoli Fan, Maojun Chen

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

Single-cell RNA sequencing reveals that MYBL2 in malignant epithelial cells is involved in the development and progression of ovarian cancer DOI Creative Commons
Wenwen Shao, Zhiheng Lin,

Zhikai Xiahou

et al.

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

Published: July 29, 2024

Ovarian carcinoma (OC) is a prevalent gynecological malignancy associated with high recurrence rates and mortality, often diagnosed at advanced stages. Despite advances in immunotherapy, immune exhaustion remains significant challenge achieving optimal tumor control. However, the exploration of intratumoral heterogeneity malignant epithelial cells ovarian cancer microenvironment still limited, hindering our comprehensive understanding disease.

Language: Английский

Citations

34
Elucidating stearoyl metabolism and NCOA4-mediated ferroptosis in gastric cancer liver metastasis through multi-omics single-cell integrative mendelian analysis: advancing personalized immunotherapy strategies DOI Creative Commons

Zhongqiu Yang,

Yuquan Chen, Yaping Miao

et al.

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

Citations

1
Unravelling infiltrating T‐cell heterogeneity in kidney renal clear cell carcinoma: Integrative single‐cell and spatial transcriptomic profiling DOI Creative Commons
Haiqing Chen,

Haoyuan Zuo,

Jinbang Huang

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(12)

Published: June 1, 2024

Abstract Kidney renal clear cell carcinoma (KIRC) pathogenesis intricately involves immune system dynamics, particularly the role of T cells within tumour microenvironment. Through a multifaceted approach encompassing single‐cell RNA sequencing, spatial transcriptome analysis and bulk profiling, we systematically explored contribution infiltrating to KIRC heterogeneity. Employing high‐density weighted gene co‐expression network (hdWGCNA), module scoring machine learning, identified distinct signature cell‐associated genes (ITSGs). Spatial transcriptomic data were analysed using robust type decomposition (RCTD) uncover interactions. Further analyses included enrichment assessments, infiltration evaluations drug susceptibility predictions. Experimental validation involved PCR experiments, CCK‐8 assays, plate cloning wound‐healing assays Transwell assays. Six subpopulations proliferating in KIRC, with notable dynamics observed mid‐ late‐stage disease progression. revealed significant correlations between epithelial across varying distances The ITSG‐based prognostic model demonstrated predictive capabilities, implicating these modulation metabolic pathways offering insights into sensitivity for 12 treatment agents. underscored functional relevance PPIB proliferation, invasion migration. Our study comprehensively characterizes T‐cell heterogeneity sequencing data. stable based on ITSGs unveils cells' potential, shedding light microenvironment avenues personalized immunotherapy.

Language: Английский

Citations

8
Mitochondrial inhibitors: a new horizon in breast cancer therapy DOI Creative Commons

Yalan Yan,

Sijie Li,

Lanqian Su

et al.

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

Published: July 4, 2024

Breast cancer, due to resistance standard therapies such as endocrine therapy, anti-HER2 therapy and chemotherapy, continues pose a major health challenge. A growing body of research emphasizes the heterogeneity plasticity metabolism in breast cancer. Because differences subtypes exhibit bias toward metabolic pathways, targeting mitochondrial inhibitors shows great potential stand-alone or adjuvant cancer therapies. Multiple therapeutic candidates are currently various stages preclinical studies clinical openings. However, specific have been shown face multiple challenges (e.g., single therapies, structure enzymes, etc.), combining with pathways may be necessary. In this paper, we review critical role functions, including oxidative phosphorylation (OXPHOS), tricarboxylic acid cycle, fatty amino metabolism, reprogramming cells. addition, outline impact dysfunction on different aiming provide additional ideas for development improve efficacy existing

Language: Английский

Citations

6
Integrated single-cell RNA sequencing reveals the tumor heterogeneity and microenvironment landscape during liver metastasis in adenocarcinoma of esophagogastric junction DOI Creative Commons

Junrui Xu,

Ussama Sadiq,

Wenxue Zhao

et al.

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

Citations

0
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 DOI Creative Commons
Guobing Wang,

Jinbang Huang,

Haiqing Chen

et al.

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

Citations

0
Epigenetic modifications in breast cancer: from immune escape mechanisms to therapeutic target discovery DOI Creative Commons
Zhihua Kang, Junlin Wang, Jiyan Liu

et al.

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

Published: April 17, 2025

Breast cancer (BC) is one of the most prevalent malignant tumors among women globally, with number cases accounting for even more than 1/3 all tumor patients in women. Recent studies have found that incidence BC increasing every year. Despite great progress made treatment, characteristics cells, such as strong immune evasion, easy recurrence and drug resistance, are still main reasons limiting survival patients. Epigenetics becoming an important method to reveal development cancer, mainly through study DNA methylation, histone modification, chromatin structure changes non-coding RNA. In addition, researchers epigenetic markers potential early detection personalized treatment BC. Inhibitors targeting epigenetically modified enzymes effective treating a wide range provide significant patient quality life. Therefore, this review will comprehensively summarize role modifications development. Second, paper focus on summarizing how induce formation microenvironment (TIME) Targeting mechanism action provides new perspectives unravel complex process development, while paving way novel diagnostic therapeutic targets. future, by integrating multi-omics data enable deeper understanding pathogenesis BC, we be able promote overall precision medicine.

Language: Английский

Citations

0
Single-cell transcriptomics reveals heterogeneity and prognostic markers of myeloid precursor cells in acute myeloid leukemia DOI Creative Commons
Guanghua He, Lai Jiang, Xuancheng Zhou

et al.

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

Published: Dec. 16, 2024

Acute myeloid leukemia (AML) is a hematologic tumor with poor prognosis and significant clinical heterogeneity. By integrating transcriptomic data, single-cell RNA sequencing data independently collected this study aims to identify key genes in AML establish prognostic assessment model improve the accuracy of prediction.

Language: Английский

Citations

2
Precision prognostication in breast cancer: unveiling a long non-coding RNA-based model linked to disulfidptosis for tailored immunotherapeutic strategies DOI Creative Commons
Cheng‐Lu Jiang,

Shengke Zhang,

Lai Jiang

et al.

Aging, Journal Year: 2024, Volume and Issue: unknown

Published: June 18, 2024

Background: Breast cancer, comprising 15% of newly diagnosed malignancies, poses a formidable global oncological challenge for women. The severity this malady stems from tumor infiltration, metastasis, and elevated mortality rates. Disulfidptosis, an emerging cellular demise mechanism, presents promising avenue precision therapy. Our aim was to construct prognostic framework centered on long non-coding RNAs (lncRNAs) associated with disulfidptosis, aiming guide the strategic use clinical drugs, enhance precision, advance immunotherapy prognosis assessment. Methods: We systematically analyzed TCGA-BRCA dataset identify disulfidptosis-linked lncRNAs. Employing co-expression analysis, we discerned significant relationships between disulfidptosis-associated genes Identified lncRNAs underwent univariate Cox regression validation through LASSO regression, culminating in identification eight signature using multivariate proportional risk model. Then, utilized selected build prediction models. Results: DAL model exhibited outstanding efficacy, establishing itself as autonomous determinant breast cancer prognosis. It adeptly differentiated low high-risk patient cohorts, individuals experiencing significantly abbreviated survival durations. Notably, these cohorts displayed marked discrepancies markers microenvironment attributes. Conclusions: has performed well assessment by combining it other traditional indicators Nomogram plots gene expression data calculate patients' disease scores. This approach provides new ideas decision support personalized treatment decisions patients different levels.

Language: Английский

Citations

1
Elucidating the multifaceted role of MGAT1 in hepatocellular carcinoma: integrative single-cell and spatial transcriptomics reveal novel therapeutic insights DOI Creative Commons
Yang Li, Yuan Chen,

Danqiong Wang

et al.

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

Published: July 16, 2024

Glycosyltransferase-associated genes play a crucial role in hepatocellular carcinoma (HCC) pathogenesis. This study investigates their impact on the tumor microenvironment and molecular mechanisms, offering insights into innovative immunotherapeutic strategies for HCC.

Language: Английский

Citations

1