IGFBP7+ subpopulation and IGFBP7 risk score in astrocytoma: insights from scRNA-Seq and bulk RNA-Seq DOI Creative Commons
Liang Zhao, Wenwen Shao,

Zhikai Xiahou

et al.

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

Published: Sept. 30, 2024

Background Glioma is the predominant malignant brain tumor that lacks effective treatment options due to its shielding by blood-brain barrier (BBB). Astrocytes play a role in development of glioma, yet diverse cellular composition astrocytoma has not been thoroughly researched. Methods We examined internal diversity seven distinct subgroups through single-cell RNA sequencing (scRNA-seq), pinpointed crucial using CytoTRACE, monocle2 pseudotime analysis, and slingshot employed various techniques identify critical subgroups, delved into communication analysis. Then, we combined clinical information GBM patients used bulk (bulk RNA-seq) analyze prognostic impact relevant molecules on patients, performed vitro experiments for validation. Results The analysis current study revealed C0 IGFBP7+ cells were noteworthy subpopulation astrocytoma, influencing differentiation progression astrocytoma. A predictive model was developed categorize high- low-scoring groups based IGFBP7 Risk Score (IGRS), with survival revealing poorer prognosis high-IGRS group. Analysis immune cell infiltration, identification genes differential expression, enrichment analyses, assessment copy number variations, evaluation drug susceptibility conducted, all which highlighted their significant influence Conclusion This research enhances comprehension delves factors impacting offers fresh perspectives treating glioma.

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
Unveiling the cellular landscape: insights from single-cell RNA sequencing in multiple myeloma DOI Creative Commons

Xinhan Li,

Zhiheng Lin,

Fu Zhao

et al.

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

Published: Aug. 30, 2024

The aim of this research was to gain a thorough understanding the processes involved in cell communication and discover potential indicators for treating multiple myeloma (MM) through use single-cell RNA sequencing (scRNA-seq). And explored expression myeloma-related subgroups on metal ion-related pathways explore relationship between MM ions.

Language: Английский

Citations

26
Single-cell RNA sequencing explored potential therapeutic targets by revealing the tumor microenvironment of neuroblastoma and its expression in cell death DOI Creative Commons
Lei Sun, Wenwen Shao, Zhiheng Lin

et al.

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

Published: Sept. 5, 2024

Language: Английский

Citations

26
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

9
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

7
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

2
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

1
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
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
Identification and functional characterization of T-cell exhaustion-associated lncRNA AL031775.1 in osteosarcoma: a novel therapeutic target DOI Creative Commons
Yameng Wang, Jinghong Yuan, Keying Guo

et al.

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

Published: Feb. 24, 2025

Osteosarcoma, an aggressive bone malignancy predominantly affecting children and adolescents, presents significant therapeutic challenges with a 5-year survival rate below 30% in metastatic cases. T-cell exhaustion, characterized by the overexpression of immune checkpoint molecules, contributes to osteosarcoma progression evasion. Although targeting these inhibitory pathways has shown potential restoring activity, molecular regulators depletion are poorly understood. This study employed comprehensive bioinformatics analyses on samples from TARGET database, combined normal tissue data GTEx identify exhaustion-associated genes their co-expressed long non-coding RNAs (lncRNAs). Gene ontology KEGG pathway were used elucidate immune-related enrichments. A six-lncRNA prognostic model was established using LASSO regression validated separate cohorts. Functional assays evaluated impact lncRNA AL031775.1 cell behavior function. Twenty-four key exhaustion-related identified significantly enriched pathways, indicating importance microenvironment. The constructed stratified patients prognosis, showing robust predictive performance across Among six lncRNAs, is notably downregulated promotes proliferation, migration, invasion while contributing exhaustion. In T cells, downregulation impairs antitumor immunity, upregulates molecules LAG3, PD1, CTLA4, diminishes cytotoxic activity against tumor cells. identifies novel highlights managing enhancing immunity counteracting progression. Targeting represents promising approach improve immunotherapy efficacy osteosarcoma. These findings provide critical insights into regulation exhaustion suggest new avenue for intervention.

Language: Английский

Citations

0