A new perspective on macrophage-targeted drug research: the potential of KDELR2 in bladder cancer immunotherapy DOI Creative Commons
Zhiyi Zhao, Hongling Jia, Zhou Sun

et al.

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

Published: Dec. 3, 2024

Bladder cancer was recognized as one of the most common malignant tumors in urinary system, and treatment options remained largely limited to conventional surgery, radiotherapy, chemotherapy, which patient benefits.

Language: Английский

Single-cell RNA sequencing and immune microenvironment analysis reveal PLOD2-driven malignant transformation in cervical cancer DOI Creative Commons
Zhiheng Lin,

Fengxin Wang,

Renwu Yin

et al.

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

Published: Jan. 7, 2025

Cervical cancer is the fourth most common in women globally, and main cause of disease has been found to be ongoing HPV infection. remains primary cancer-related death despite major improvements screening treatment approaches, especially low- middle-income nations. Therefore, it crucial investigate tumor microenvironment advanced cervical order identify possible targets. In better understand malignant epithelial cells (EPCs), this study used bulk RNA-seq data from UCSC conjunction with single-cell RNA sequencing ArrayExpress database. After putting quality control procedures into place, cell type identification clustering analysis using Seurat software were carried out. To clarify functional pathways, enrichment differential gene expression The CIBERSORT ESTIMATE R packages evaluate immune characteristics, univariate multivariate Cox regression analyses extract prognostic features. Furthermore, assessments drug sensitivity Eight types identified, EPCs showing high proliferative stemness Five EPC subpopulations defined, C1 NNMT+ CAEPCs driving differentiation. A NNMT Risk Score (NCRS) model was developed, revealing a correlation between elevated NCRS scores adverse patient outcomes characterized by evasion. vitro experiments validated that PLOD2 significantly enhances proliferation, migration, invasion cells. This investigation delineated eight five cancer, establishing as therapeutic target. demonstrated its capability, indicating higher are associated poorer clinical outcomes. validation highlights potential, underscoring critical need for integrating immunotherapy targeted strategies enhance diagnostic approaches cancer.

Language: Английский

Citations

11

MAZ-mediated tumor progression and immune evasion in hormone receptor-positive breast cancer: Targeting tumor microenvironment and PCLAF+ subtype-specific therapy DOI
Gaofeng Ni,

Yuwei Sun,

Hongling Jia

et al.

Translational Oncology, Journal Year: 2025, Volume and Issue: 52, P. 102280 - 102280

Published: Jan. 13, 2025

Language: Английский

Citations

8

Characterizing tumor biology and immune microenvironment in high-grade serous ovarian cancer via single-cell RNA sequencing: insights for targeted and personalized immunotherapy strategies DOI Creative Commons
Fu Zhao,

Xiaojing Jiang,

Yumeng Li

et al.

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

Published: Jan. 17, 2025

High-grade serous ovarian cancer (HGSOC), the predominant subtype of epithelial cancer, is frequently diagnosed at an advanced stage due to its nonspecific early symptoms. Despite standard treatments, including cytoreductive surgery and platinum-based chemotherapy, significant improvements in survival have been limited. Understanding molecular mechanisms, immune landscape, drug sensitivity HGSOC crucial for developing more effective personalized therapies. This study integrates insights from immunology, profiling, analysis identify novel therapeutic targets improve treatment outcomes. Utilizing single-cell RNA sequencing (scRNA-seq), systematically examines tumor heterogeneity microenvironment, focusing on biomarkers influencing response activity, aiming enhance patient outcomes quality life. scRNA-seq data was obtained GEO database this study. Differential gene expression analyzed using ontology set enrichment methods. InferCNV identified malignant cells, while Monocle, Cytotrace, Slingshot software inferred differentiation trajectories. The CellChat package predicted cellular communication between cell subtypes other pySCENIC utilized transcription factor regulatory networks within subtypes. Finally, results were validated through functional experiments, a prognostic model developed assess prognosis, infiltration, across various risk groups. investigated scRNA-seq, their interactions microenvironment. We confirmed key role C2 IGF2+ HGSOC, which significantly associated with poor prognosis high levels chromosomal copy number variations. located terminal tumor, displaying higher degree malignancy close association IIIC tissue types. also metabolic pathways, such as glycolysis riboflavin metabolism, well programmed death processes. highlighted complex fibroblasts MK signaling pathway, may be closely related tumor-associated progression. Elevated PRRX1 connected impact disease progression by modulating transcription. A based demonstrated adverse outcomes, emphasizing importance infiltration clinical intervention strategies. oncology, immunotherapy, reveal mechanisms driving resistance. subtype, linked offers promising target future Emphasizing sensitivity, research highlights strategies life patients.

Language: Английский

Citations

3

Inhibition of programmed cell death by melanoma cell subpopulations reveals mechanisms of melanoma metastasis and potential therapeutic targets DOI Creative Commons
Yuepeng An,

Fu Zhao,

Hongling Jia

et al.

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

Published: Jan. 20, 2025

Melanoma is an aggressive type of skin cancer that arises from melanocytes, the cells responsible for producing pigment. In contrast to non-melanoma cancers like basal cell carcinoma and squamous carcinoma, melanoma more invasive. was distinguished by its rapid progression, high metastatic potential, significant resistance conventional therapies. Although it accounted a small proportion cases, accounts majority deaths caused due ability invade deep tissues, adapt diverse microenvironments, evade immune responses. These unique features highlighted challenges treating underscored importance advanced tools, such as single-cell sequencing, unravel biology develop personalized therapeutic strategies. Thus, we conducted analysis cellular composition within tumor tissues further subdivided into subpopulations. Through analyzing metabolic pathways, stemness genes, transcription factors (TFs) among in different phases (G1, G2/M, S) well between primary foci cells, investigated specific mechanisms underlying metastasis. We also revisited temporal trajectories subpopulations, identifying core subpopulation C0 SOD3 + cells. Our findings revealed close relationship pivotal oxidative pathways tissues. Additionally, analyzed prognostically relevant differentially expressed genes (DEGs) built predictive model associated with outcomes. selected gene IGF1 highest coefficient (coef) value analysis, experimentally validated essential function proliferation invasive metastasis melanoma. infiltration discovered critical roles played M1/M2 macrophages progression evasion. Furthermore, development malignant were closely various forms programmed death (PCD), including apoptosis, autophagic death, ferroptosis, pyroptosis. often resisted mechanisms, maintaining their growth inhibiting apoptosis evading death. Meanwhile, induction ferroptosis pyroptosis thought trigger responses helped suppress dissemination. A deeper understanding PCD provided foundation developing novel targeted therapies, potential enhance treatment efficacy. contributed prognostic models shed light on research directions concerning targets.

Language: Английский

Citations

2

Heterogeneity of cancer-associated fibroblast subpopulations in prostate cancer: Implications for prognosis and immunotherapy DOI Creative Commons
Chen Ding, Jian‐Ge Wang, Jie Wang

et al.

Translational Oncology, Journal Year: 2024, Volume and Issue: 52, P. 102255 - 102255

Published: Dec. 24, 2024

Language: Английский

Citations

7

A novel mitochondrial-related risk model for predicting prognosis and immune checkpoint blockade therapy response in uterine corpus endometrial carcinoma DOI Creative Commons
Rachel G. Liao,

Jinhong Wang,

Fan Zhang

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 9, 2025

Uterine Corpus Endometrial Carcinoma (UCEC) represents a common malignant neoplasm in women, with its prognosis being intricately associated available therapeutic interventions. In the past few decades, there has been burgeoning interest role of mitochondria within context UCEC. Nevertheless, development and application prognostic models predicated on mitochondrial-related genes (MRGs) UCEC remains exploratory stages. This study utilized RNA sequencing data clinical information from TCGA database to identify differentially expressed MRGs (DEMRGs) between normal groups that are overall survival (OS). Patients were randomly assigned training testing cohorts 1:1 ratio. cohort, risk model based DEMRGs was developed using Lasso Cox regression analysis. Subsequently, patients both stratified into high-risk low-risk their median scores. The performance validated through Kaplan-Meier analysis, ROC curves, nomograms. Additionally, further analyses including functional enrichment, immune landscape assessment, prediction response ICB therapy, mutation profiling, drug sensitivity analysis elucidated biological distinctions identified groups. We established incorporating eight MRGs. classified he group exhibited significantly poorer prognoses relative those group. Functional enrichment substantial differences processes signaling pathways cohorts. Immune showed elevated scores significant immunosuppressive evasion mechanisms. Conversely, higher expression human leukocyte antigen (HLA) family members checkpoint (ICGs) compared counterparts.Consequently, greater responsiveness immunotherapy potential small molecule drugs, whereas more susceptible chemotherapy. formulated this demonstrates efficacy predicting UCEC, thereby providing scientific basis for personalized treatment strategies. Future research endeavors should focus validating utility investigate specific mechanisms

Language: Английский

Citations

1

Progress in immune microenvironment, immunotherapy and prognostic biomarkers in pediatric osteosarcoma DOI Creative Commons
Lin Zhang,

Haoming Jiang,

Hongzhi Ma

et al.

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

Published: Jan. 22, 2025

Pediatric osteosarcoma, the most prevalent primary malignant bone tumor in children, is marked by aggressive progression and a generally poor prognosis. Despite advances treatment, including multi-agent chemotherapy, survival rates remain suboptimal, with metastasis, particularly to lungs, contributing significantly mortality. The microenvironment plays crucial role osteosarcoma progression, immune cells such as tumor-associated macrophages T lymphocytes influencing behavior. immunosuppressive environment, dominated M2 macrophages, contributes evasion therapeutic outcomes, though recent findings suggest potential for reprogramming these enhance responses. This review provides comprehensive overview of landscape pediatric focus on their interactions within (TME). It examines impact checkpoints, genetic mutations, inflammatory pathways highlighting contribution disease advancement. Additionally, emerging immunotherapeutic strategies, checkpoint inhibitors, macrophage reprogramming, antibody-based therapies, are summarized detail, showcasing improve outcomes.

Language: Английский

Citations

1

Carboplatin-resistance-related DNA damage repair prognostic gene signature and its association with immune infiltration in breast cancer DOI Creative Commons
Shuwen Dong, Anqi Li, Ruijun Pan

et al.

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

Published: Jan. 29, 2025

Introduction Breast cancer is among the most prevalent malignant tumors globally, with carboplatin serving as a standard treatment option. However, resistance often compromises its efficacy. DNA damage repair (DDR) pathways are crucial in determining responses to and also associated immune infiltration. This study aimed identify DDR genes involved elucidate their effects on prognosis, infiltration, drug sensitivity breast patients. Methods A 3D-culture model resistant was constructed sequenced. Co-expressed were analyzed develop predictive model. Immune infiltration analysis tools employed assess microenvironment of patients varying expression levels these risk genes. Additionally, predictions made evaluate efficacy other damage-related drugs across different groups. Molecular assays performed investigate role key gene TONSL cancer. Results By integrating data from public database, we established prognostic signature comprising thirteen Our indicated that this patterns patients, particularly concerning CD8+ T cells NK cells. it demonstrated significant correlation DDR-related drugs, suggesting potential biomarker for Compared control group, TONSL-knockdown cell lines exhibited diminished response DNA-damaging agents, marked by notable increase enhanced sensitivity. Furthermore, single-cell revealed elevated dendritic epithelial cells, triple-negative cancers. Conclusions Carboplatin resistance-related may serve therapeutic target cancer, indicating new strategies

Language: Английский

Citations

1

Single-cell RNA sequencing revealed PPARG promoted osteosarcoma progression: based on osteoclast proliferation DOI Creative Commons
Lei Sun, Jinhao Zhang,

Zhikai Xiahou

et al.

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

Published: Jan. 28, 2025

Background Osteosarcoma (OS) is one of the most common primary malignant bone tumors, primarily originating from mesenchymal tissue. It notorious for its high invasiveness, disability rate, mortality and poor prognosis. In metastatic destruction can promote cancer progression, which closely related to osteoclast activation imbalance between osteoblasts osteoclasts. A large number studies confirmed that osteoclasts are an important part OS, play active role in destroying homeostasis promoting progress OS. Therefore, we conducted a detailed study at single cell level, aiming find new OS therapeutic targets prevent tumor progression local spread. Methods We analyzed single-cell sequencing data patients usedMonocle2, Cytotrace, Slingshot software analyze pseudo-sequential trajectory during progression. CellChat was used reveal communication cells. PySCENIC identify transcription factors Finally, further demonstrated results by RT-qPCR analysis, CCK-8 assay, wound healing Transwell etc. Results Through analysis identified highly specific subgroup, C2MKI67+ Osteoclast. The key signaling pathway APP top 1 factor PPARG this subgroup played essential roles proliferation differentiation. Given pivotal speculated these pathways could emerge as novel targets, offering innovative strategies treatment. Conclusion This enhanced our understanding through scRNA-seq. Furthermore, discovered amplifies proliferation, resulting excessive resorption degradation matrix, thereby creating favorable environment growth. By innovatively targeting PPARG, it affected thus progression; work offered insights directions clinical treatment patients.

Language: Английский

Citations

0

Sesquiterpene lactones and cancer: new insight into antitumor and anti-inflammatory effects of parthenolide-derived Dimethylaminomicheliolide and Micheliolide DOI Creative Commons
Jian Li, Xin Li, Hongwei Liu

et al.

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

Published: Feb. 20, 2025

The isolation and application of biological macromolecules (BMMs) have become central in applied science today, with these compounds serving as anticancer, antimicrobial, anti-inflammatory agents. Parthenolide (PTL), a naturally occurring sesquiterpene lactone derived from Tanacetum parthenium (feverfew), is among the most important BMMs. PTL has been extensively studied for its anticancer properties, making it promising candidate further research drug development. This review summarizes effects derivatives, focus on Micheliolide (MCL) Dimethylaminomicheliolide (DMAMCL). These compounds, PTL, developed to overcome PTL's instability acidic basic conditions low solubility. We also explore their potential targeted combination therapies, providing comprehensive overview therapeutic mechanisms highlighting significance future cancer treatment strategies.

Language: Английский

Citations

0