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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Single-cell and bulk RNA sequencing reveal cancer-associated fibroblast heterogeneity and a prognostic signature in prostate cancer

Medicine, Journal Year: 2023, Volume and Issue: 102(32), P. e34611 - e34611

Published: Aug. 11, 2023

Cancer-associated fibroblasts (CAFs), the central players in tumor microenvironment (TME), can promote progression and metastasis via various functions. However, properties of CAFs prostate cancer (PCa) have not been fully assessed. Therefore, we aimed to examine CAF characteristics PCa construct a CAF-derived signature predict prognosis. were identified using single-cell RNA sequencing (scRNA-seq) data from 3 studies. We performed FindAllMarkers function extract marker genes constructed biochemical relapse-free survival (bRFS) Cancer Genome Atlas (TCGA) cohort. Subsequently, different algorithms applied reveal differences TME, immune infiltration, treatment responses high- low-risk groups. Additionally, heterogeneity was assessed PCa, which confirmed by functional enrichment analysis, gene set analysis (GSEA), AUCell method. The scRNA-seq cluster with 783 cells determined 183 genes. Cell-cell communication revealed extensive interactions between cells. A CAF-related prognostic model, containing 7 (ASPN, AEBP1, ALDH1A1, BGN, COL1A1, PAGE4 RASD1), developed bRFS validated 4 independent bulk RNA-seq cohorts. Moreover, high-risk group score connected an immunosuppressive such as higher level M2 macrophages lower levels plasma CD8+ T cells, reduced reaction rate for immunotherapy compared group. After re-clustering unsupervised clustering, biologically distinct subsets, namely myofibroblast-like (myCAFs), inflammatory (iCAFs) antigen-presenting (apCAFs). In conclusion, signature, first its kind, effectively prognosis serve indicator immunotherapy. Furthermore, our study subpopulations functions PCa.

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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Unveiling the role of regulatory T cells in the tumor microenvironment of pancreatic cancer through single-cell transcriptomics and in vitro experiments

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

Published: Sept. 11, 2023

In order to investigate the impact of Treg cell infiltration on immune response against pancreatic cancer within tumor microenvironment (TME), and identify crucial mRNA markers associated with cells in cancer, our study aims delve into role anti-tumor cancer.The ordinary transcriptome data for this was sourced from GEO TCGA databases. It analyzed using single-cell sequencing analysis machine learning. To assess level tissues, we employed CIBERSORT method. The identification genes most closely accomplished through implementation weighted gene co-expression network (WGCNA). Our involved various quality control methods, followed by annotation advanced analyses such as trajectory communication elucidate microenvironment. Additionally, categorized two subsets: Treg1 favorable prognosis, Treg2 poor based enrichment scores key genes. Employing hdWGCNA method, these subsets critical signaling pathways governing their mutual transformation. Finally, conducted PCR immunofluorescence staining vitro validate identified genes.Based results analysis, observed significant Subsequently, utilizing WGCNA learning algorithms, ultimately four cell-related (TRGs), among which exhibited correlations occurrence progression cancer. Among them, CASP4, TOB1, CLEC2B were poorer prognosis patients, while FYN showed a correlation better prognosis. Notably, differences found HIF-1 pathway between These conclusions further validated experiments.Treg played microenvironment, presence held dual significance. Recognizing characteristic vital understanding limitations cell-targeted therapies. FYN, close associations infiltrating suggesting involvement functions. Further investigation warranted uncover mechanisms underlying associations. emerged contributing duality cells. Targeting could potentially revolutionize existing treatment approaches

Language: Английский

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Disulfidptosis as a key regulator of glioblastoma progression and immune cell impairment

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

Published: Jan. 30, 2025

Background Glioblastoma, associated with poor prognosis and impaired immune function, shows potential interactions between newly identified disulfidptosis mechanisms T cell exhaustion, yet these remain understudied. Methods Key genes were using Lasso regression, followed by multivariate analysis to develop a prognostic model. Single-cell pseudotemporal explored T-cell exhaustion (Tex) signaling in differentiation. Immune infiltration was assessed via ssGSEA, while transwell assays immunofluorescence examined the effects of disulfidptosis-Tex on glioma behavior response. Results Eleven found critical for glioblastoma survival outcomes. This gene set underpinned model predicting patient prognosis. showed high activity endothelial cells. Memory populations linked genes. SMC4 inhibition reduced LN299 migration increased chemotherapy sensitivity, decreasing CD4 CD8 activation. Conclusions Disulfidptosis-Tex are pivotal progression interactions, offering new avenues improving anti-glioblastoma therapies through modulation exhaustion.

Language: Английский

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Circulating cell-free DNA methylation analysis of pancreatic cancer patients for early noninvasive diagnosis

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

Published: March 10, 2025

Background Aberrant hypermethylation of genomic DNA CpG islands (CGIs) is frequently observed in human pancreatic cancer (PAC). A plasma cell-free (cfDNA) methylation analysis method can be utilized for the early and noninvasive detection PAC. This study also aimed to differentiate PAC from other types. Methods We employed methylated tandem amplification sequencing (MCTA-Seq) method, which targets approximately one-third CGIs, on samples patients (n = 50) healthy controls 52), as well cancerous adjacent noncancerous tissue 66). The method’s efficacy detecting distinguishing it hepatocellular carcinoma (HCC), colorectal (CRC), gastric (GC) was evaluated. Additionally, a score typing system established. Results identified total 120 cfDNA biomarkers, including IRX4 , KCNS2 RIMS4 blood. panel comprising these biomarkers achieved sensitivity 97% 86% discovery validation cohorts, respectively, with specificity 100% both cohorts. scoring systems were clinically applicable. Furthermore, we hundreds differentially between HCC, CRC, GC. Certain combinations markers used highly specific (approximately 100%) algorithm GC Conclusions Our PAC, offering novel approach early, diagnosis

Language: Английский

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Uncovering the heterogeneity of NK cells on the prognosis of HCC by integrating bulk and single-cell RNA-seq data

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

Published: March 18, 2025

The tumor microenvironment (TME) plays a critical role in the development, progression, and clinical outcomes of hepatocellular carcinoma (HCC). Despite natural killer (NK) cells immunity, there is limited research on their status within HCC. In this study, single-cell RNA sequencing (scRNA-seq) analysis HCC datasets was performed to identify potential biomarkers investigate involvement TME. Single-cell data were extracted from GSE149614 dataset processed for quality control using "Seurat" package. subtypes TCGA classified through consensus clustering based differentially expressed genes (DEGs). Weighted gene co-expression network (WGCNA) employed construct networks. Furthermore, univariate multivariate Cox regression analyses conducted variables linked overall survival. single-sample set enrichment (ssGSEA) used analyze immune screened genes. A total 715 DEGs 864 identified, with 25 overlapping found between two datasets. prognostic risk score model then established. Significant differences cell infiltration observed high-risk low-risk groups. Immunohistochemistry showed that HRG expression decreased compared normal tissues, whereas TUBA1B elevated Our study identified two-gene signature NK markers highlighted TME, which may offer novel insights immunotherapy strategies. Additionally, we developed an accurate reliable model, combining factors aid clinicians decision-making.

Language: Английский

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Development and validation of a nomogram model of lung metastasis in breast cancer based on machine learning algorithm and cytokines

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 14, 2025

The relationship between cytokines and lung metastasis (LM) in breast cancer (BC) remains unclear current clinical methods for identifying (BCLM) lack precision, thus underscoring the need an accurate risk prediction model. This study aimed to apply machine learning algorithms key factors BCLM before developing a reliable model centered on cytokines. population-based retrospective included 326 BC patients admitted Second Affiliated Hospital of Xuzhou Medical University September 2018 2023. After randomly assigning training cohort (70%; n = 228) or validation (30%; 98) were identified using Least Absolute Shrinkage Selection Operator (LASSO), Extreme Gradient Boosting (XGBoost) Random Forest (RF) models. Significant visualized with Venn diagram incorporated into nomogram model, performance which was then evaluated according three criteria, namely discrimination, calibration utility plots, receiver operating characteristic (ROC) curves decision curve analysis (DCA). Among cohort, 70 developed LM. A predict 5-year 10-year by incorporating five variables, endocrine therapy, hsCRP, IL6, IFN-ɑ TNF-ɑ. For cohorts had AUC values 0.786 (95% CI: 0.691-0.881) 0.627 0.441-0.813), respectively, while corresponding 0.687 0.528-0.847) 0.797 0.605-0.988), respectively. ROC further confirmed model's strong discriminative ability, plots indicated that predicted observed outcomes good agreement both cohorts. Finally, DCA demonstrated effectiveness practice. Using algorithms, this aa could effectively identify who at higher LM, providing valuable tool decision-making settings.

Language: Английский

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The malignant signature gene of cancer-associated fibroblasts serves as a potential prognostic biomarker for colon adenocarcinoma patients

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

Published: April 17, 2025

Colon adenocarcinoma (COAD) is the most frequently occurring type of colon cancer. Cancer-associated fibroblasts (CAFs) are pivotal in facilitating tumor growth and metastasis; however, their specific role COAD not yet fully understood. This research utilizes single-cell RNA sequencing (scRNA-seq) to identify validate gene markers linked malignancy CAFs. ScRNA-seq data was downloaded from a database subjected quality control, dimensionality reduction, clustering, cell annotation, communication analysis, enrichment specifically focusing on tissues compared normal tissues. Fibroblast subsets were isolated, dimensionally reduced, clustered, then combined with copy number variation (CNV) inference pseudotime trajectory analysis genes related malignancy. A Cox regression model constructed based these genes, incorporating LASSO nomogram construction, validation.Subsequently, we established two FNDC5-knockdown lines utilized colony formation transwell assays investigate impact FNDC5 cellular biological behaviors. Using scRNA-seq data, analyzed 8,911 cells samples, identifying six distinct types. Cell highlighted interactions between types mediated by ligands receptors. CNV classified CAFs into three groups levels. Pseudo-time identified 622 pseudotime-related generated forest plot using univariate regression. Lasso independent prognostic FNDC5, which visualized nomogram. Kaplan-Meier survival confirmed value showing associations T stage distant metastasis. In vitro experiment results demonstrated strong association expression levels proliferative, migratory, invasive abilities cancer cells. We developed risk for as potential therapeutic target COAD.

Language: Английский

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Metabolic reprogramming and immune microenvironment characteristics in laryngeal carcinoma: advances in immunotherapy

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

Published: April 30, 2025

Laryngeal squamous cell carcinoma (LSCC) is a prevalent malignancy with high mortality and recurrence rates, necessitating novel therapeutic strategies. Recent research highlights the pivotal role of metabolic reprogramming immune microenvironment alterations in LSCC pathogenesis, providing promising avenues for targeted therapy. This review summarizes characteristics LSCC, including glycolysis, lipid metabolism, amino acid biosynthesis, their implications tumor progression resistance. Additionally, this further describes microenvironment’s immunosuppressive landscape, checkpoint regulation, tumor-associated macrophages, T-cell dysfunction. The integration immune-targeted strategies represents frontier treatment, warranting investigation.

Language: Английский

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