Decoding the tumor microenvironment and molecular mechanism: unraveling cervical cancer subpopulations and prognostic signatures through scRNA-Seq and bulk RNA-seq analyses

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

Published: Feb. 28, 2024

Background Cervical carcinoma (CC) represents a prevalent gynecological neoplasm, with discernible rise in prevalence among younger cohorts observed recent years. Nonetheless, the intrinsic cellular heterogeneity of CC remains inadequately investigated. Methods We utilized single-cell RNA sequencing (scRNA-seq) transcriptomic analysis to scrutinize tumor epithelial cells derived from four specimens cervical patients. This method enabled identification pivotal subpopulations and elucidation their contributions progression. Subsequently, we assessed influence associated molecules bulk (Bulk RNA-seq) performed experiments for validation purposes. Results Through our analysis, have discerned C3 PLP2+ Tumor Epithelial Progenitor Cells as noteworthy subpopulation (CC), exerting on differentiation progression CC. established an independent prognostic indicator—the EPCs score. By stratifying patients into high low score groups based median score, that high-score group exhibits diminished survival rates compared low-score group. The correlations between these immune infiltration, enriched pathways, single-nucleotide polymorphisms (SNPs), drug sensitivity, other factors, further underscore impact prognosis. Cellular validated significant ATF6 proliferation migration cell lines. Conclusion study enriches comprehension determinants shaping CC, elevates cognizance microenvironment offers valuable insights prospective therapies. These discoveries contribute refinement diagnostics formulation optimal therapeutic approaches.

Language: Английский

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The integrated single-cell analysis developed an immunogenic cell death signature to predict lung adenocarcinoma prognosis and immunotherapy

Aging, Journal Year: 2023, Volume and Issue: 15(19), P. 10305 - 10329

Published: Oct. 4, 2023

Background: Research on immunogenic cell death (ICD) in lung adenocarcinoma (LUAD) has been relatively limited. This study aims to create ICD-related signatures for accurate survival prognosis prediction LUAD patients, addressing the challenge of lacking reliable early prognostic indicators this type cancer. Methods: Using single-cell RNA sequencing (scRNA-seq) analysis, ICD activity cells was calculated by AUCell algorithm, divided into high- and low-ICD groups according median values, key regulatory genes were identified through differential these integrated TCGA data construct using LASSO COX regression multi-dimensional analysis terms prognosis, immunotherapy, tumor microenvironment (TME), mutational landscape. Results: The constructed signature reveals a pronounced disparity between low-risk patients. statistical discrepancies times among patients from both GEO databases further corroborate observation. Additionally, heightened levels immune infiltration expression are evidenced group, suggesting potential benefit immunotherapeutic interventions pivotal risk-associated tissue samples assessed utilizing qRT-PCR, thereby unveiling PITX3 as plausible therapeutic target context LUAD. Conclusions: Our provide help predicting immunotherapy some extent guide clinical treatment

Language: Английский

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Common immunological and prognostic features of lung and bladder cancer via smoking‐related genes: PRR11 gene as potential immunotherapeutic target

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(10)

Published: May 1, 2024

Abstract Smoking is a well‐known risk factor for non‐small‐cell lung cancer (NSCLC) and bladder urothelial carcinoma (BLCA). Despite this, there has been no investigation into prognostic marker based on smoking‐related genes that could universally predict prognosis in these cancers correlate with immune checkpoint therapy. This study aimed to identify differential NSCLC BLCA, analyse their roles patient therapy through subgroup analyses, shed light PRR11 as crucial gene both cancers. By examining co‐expressed genes, model was constructed its impact immunotherapy BLCA evaluated. Molecular docking tissue microarray analyses were conducted explore the correlation between reciprocal SPDL1. Additionally, miRNAs associated analysed. The confirmed strong link prognosis, BLCA. identified key smoking‐associated influences efficacy of by modulating stemness A established value validated NSCLC. Furthermore, it found regulates PDL1 via SPDL1, impacting immunotherapeutic involvement hsa‐miR‐200b‐3p regulation SPDL1 expression also highlighted. Overall, elucidates modulates influencing interaction potential upstream hsa‐miR‐200b‐3p.

Language: Английский

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Current therapies and progress in the treatment of advanced gastric cancer

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Feb. 26, 2024

Gastric cancer (GC) remains one of the most life-threatening disease worldwide with poor prognosis because absence effective treatment and delay in diagnosis. Due to diagnosis, a large proportion GC patients are diagnosed as advanced GC, extreme short lifespan. In past few years, some pivotal progress novel therapies was proposed, conducted into clinical researches practice. this study, we summarized development several immunotherapy or targeted modalities for including immune checkpoint inhibitors, anti-angiogenic therapy vaccines. Additionally, advantage potential weakness each these therapeutic methods also listed. Finally, discussed promising research direction treatment, limitation basic combination therapy.

Language: Английский

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Progress in immune microenvironment, immunotherapy and prognostic biomarkers in pediatric osteosarcoma

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

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Uncovering the immune microenvironment and molecular subtypes of hepatitis B-related liver cirrhosis and developing stable a diagnostic differential model by machine learning and artificial neural networks

Frontiers in Molecular Biosciences, Journal Year: 2023, Volume and Issue: 10

Published: Sept. 22, 2023

Background: Hepatitis B-related liver cirrhosis (HBV-LC) is a common clinical disease that evolves from chronic hepatitis B (CHB). The development of can be suppressed by pharmacological treatment. When CHB progresses to HBV-LC, the patient's quality life decreases dramatically and drug therapy ineffective. Liver transplantation most effective treatment, but lack donor required for transplantation, high cost procedure post-transplant rejection make this method unsuitable patients. Methods: aim study was find potential diagnostic biomarkers associated with HBV-LC bioinformatics analysis classify into specific subtypes consensus clustering. This will provide new perspective early diagnosis, treatment prevention HCC in Two study-relevant datasets, GSE114783 GSE84044, were retrieved GEO database. We screened feature genes using differential analysis, weighted gene co-expression network (WGCNA), three machine learning algorithms including least absolute shrinkage selection operator (LASSO), support vector recursive elimination (SVM-RFE), random forest (RF) total five methods. After that, we constructed an artificial neural (ANN) model. A cohort consisting GSE123932, GSE121248 GSE119322 used external validation. To better predict risk development, also built nomogram And multiple enrichment analyses samples performed understand biological processes which they significantly enriched. different analyzed Immune infiltration approach. Results: Using data downloaded GEO, developed ANN model based on six genes. clustering classified them two subtypes, C1 C2, it hypothesized patients subtype C2 might have milder symptoms immune analysis. Conclusion: column line graphs showed excellent predictive power, providing diagnosis possible HBV-LC. delineation facilitate future

Language: Английский

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Unravelling infiltrating T‐cell heterogeneity in kidney renal clear cell carcinoma: Integrative single‐cell and spatial transcriptomic profiling

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

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Noval advance of histone modification in inflammatory skin diseases and related treatment methods

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 3, 2024

Inflammatory skin diseases are a group of caused by the disruption tissue due to immune system disorders. Histone modification plays pivotal role in pathogenesis and treatment chronic inflammatory diseases, encompassing wide range conditions, including psoriasis, atopic dermatitis, lupus, systemic sclerosis, contact lichen planus, alopecia areata. Analyzing histone as significant epigenetic regulatory approach holds great promise for advancing our understanding managing these complex Additionally, therapeutic interventions targeting modifications have emerged promising strategies effectively This comprehensive review provides an overview diverse types modification. We discuss intricate association between prevalent diseases. also current potential approaches that revolve around modulating modifications. Finally, we investigated prospects research on context paving way innovative improved patient outcomes.

Language: Английский

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Unveiling efferocytosis-related signatures through the integration of single-cell analysis and machine learning: a predictive framework for prognosis and immunotherapy response in hepatocellular carcinoma

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: July 27, 2023

Hepatocellular carcinoma (HCC) represents a prominent gastrointestinal malignancy with grim clinical outlook. In this regard, the discovery of novel early biomarkers holds substantial promise for ameliorating HCC-associated mortality. Efferocytosis, vital immunological process, assumes central position in elimination apoptotic cells. However, comprehensive investigations exploring role efferocytosis-related genes (EFRGs) HCC are sparse, and their regulatory influence on immunotherapy targeted drug interventions remain poorly understood.RNA sequencing data characteristics patients were acquired from TCGA database. To identify prognostically significant HCC, we performed limma package conducted univariate Cox regression analysis. Subsequently, machine learning algorithms employed to hub genes. assess landscape different subtypes, CIBERSORT algorithm. Furthermore, single-cell RNA (scRNA-seq) was utilized investigate expression levels ERFGs immune cells explore intercellular communication within tissues. The migratory capacity evaluated using CCK-8 assays, while sensitivity prediction reliability determined through wound-healing assays.We have successfully identified set nine genes, termed EFRGs, that hold potential establishment hepatocellular carcinoma-specific prognostic model. leveraging individual risk scores derived model, able stratify into two distinct groups, unveiling notable disparities terms infiltration patterns response immunotherapy. Notably, model's accurately predict responses substantiated experimental investigations, encompassing assay, CCK8 experiments HepG2 Huh7 cell lines.We constructed an EFRGs model serves as valuable tools assessment decision-making support context chemotherapy.

Language: Английский

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Experimentally validated oxidative stress -associated prognostic signatures describe the immune landscape and predict the drug response and prognosis of SKCM

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

Published: April 10, 2024

Skin Cutaneous Melanoma (SKCM) incidence is continually increasing, with chemotherapy and immunotherapy being among the most common cancer treatment modalities. This study aims to identify novel biomarkers for response in SKCM explore their association oxidative stress.

Language: Английский

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