Single-cell Atlas reveals core function of CPVL/MSR1 expressing macrophages in the prognosis of triple-negative breast cancer DOI Creative Commons

Xin’an Wang,

Lin Li, Xue Zhang

et al.

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

Published: Dec. 24, 2024

Background Triple-negative breast cancer (TNBC) is the most aggressive subtype of cancer, with worst prognosis among all subtypes. The impact distinct cell subpopulations within tumor microenvironment (TME) on TNBC patient has yet to be clarified. Methods Utilizing single-cell RNA sequencing (scRNA-seq) integrated bulk (bulk RNA-seq), we applied Cox regression models compute hazard ratios, and cross-validated prognostic scoring using a GLMNET-based model. Cell communication analysis was used elucidate potential mechanisms CPVL MSR1. Ultimately, interference-mediated gene knockdown utilized validate specific genes polarization tumor-associated macrophages (TAMs). Results Our findings revealed that function immune cells more pivotal in prognosis, TAMs showing strongest correlation outcomes, compared other cells. Additionally, identified MSR1 as critical TAMs, expression positively correlated favorable outcomes associated poorer prognosis. Mechanistically, may contribute by inhibiting SPP1-CD44 ligand-receptor promoting CXCL9-CXCR3, C3-C3AR1 ligand-receptor, through which interact such monocytes, neutrophils, T Moreover, cytokines including IL-18, IFNγR1, CCL20, CCL2, along complement-related like TREM2 complement component CFD, participate process or regulating macrophage polarization. Furthermore, RT-PCR experiments confirmed M1-like TAM polarization, while linked M2-like Finally, significance these two also validated HER2-positive Conclusions are biomarkers for macrophage-mediated suggesting therapeutic targeting TNBC.

Language: Английский

SPP1 macrophages across diseases: A call for reclassification? DOI Creative Commons
Alessio Reggio, Claudia Fuoco, Rebecca Deodati

et al.

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(5)

Published: March 6, 2025

SPP1+ macrophages, characterized by elevated expression of the osteopontin gene (secreted phosphoprotein 1, SPP1), have emerged as key players in various pathological contexts, including aging, chronic inflammatory diseases, and cancer. While frequently classified a subclass tumor-associated macrophages oncological settings, their presence noncancer conditions, such aging-related disorders muscular suggests broader role beyond tumors. These share conserved traits, fibrosis promotion, extracellular matrix remodeling, immune modulation, often linked to poor clinical outcomes. This perspective explores multifaceted roles across diseases advocates for reclassification distinct macrophage subtype associated with or prolonged inflammation. Recognizing cross-disease relevance could reshape biology inform targeted therapeutic strategies.

Language: Английский

Citations

1
Single‐cell transcriptome sequencing reveals SPP1‐CD44‐mediated macrophage–tumor cell interactions drive chemoresistance in TNBC DOI Creative Commons
Fuzhong Liu, Junfeng Zhang,

Xiaowei Gu

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(13)

Published: July 1, 2024

Abstract Triple‐negative breast cancer (TNBC) is often considered one of the most aggressive subtypes cancer, characterized by a high recurrence rate and low overall survival (OS). It notorious for posing challenges related to drug resistance. While there has been progress in TNBC research, mechanisms underlying chemotherapy resistance remain largely elusive. We collect single‐cell RNA sequencing (scRNA‐seq) data from five patients susceptible resistant cases. Comprehensive analyses involving copy number variation (CNV), pseudotime trajectory, cell–cell interactions, pseudospace analysis, as well transcription factor functional enrichment are conducted specifically on macrophages malignant cells. Furthermore, we performed validation experiments clinical samples using multiplex immunofluorescence. identified subset SPP1 + that secrete signals interacting with CD44 cell surfaces, potentially activating PDE3B pathway within cells via integrin pathway, leading The abnormally enhanced signal between may serve promoting patients. Therefore, could therapeutic target reduce

Language: Английский

Citations

7
Identification of cancer cell-intrinsic biomarkers associated with tumor progression and characterization of SFTA3 as a tumor suppressor in lung adenocarcinomas DOI Creative Commons
Yu Zhao, Chengcheng Zhou, Ling Zuo

et al.

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

Published: Jan. 8, 2025

Recent advancements in contemporary therapeutic approaches have increased the survival rates of lung cancer patients; however, long-term benefits remain constrained, underscoring pressing need for novel biomarkers. Surfactant-associated 3 (SFTA3), a long non-coding RNA predominantly expressed normal epithelial cells, plays crucial role development. Nevertheless, its function adenocarcinoma (LUAD) remains inadequately understood. Single-cell sequencing data were utilized to identify cell-intrinsic gene signatures associated with progression LUAD, and their roles LUAD comprehensively analyzed. Serum samples collected quantify expression levels SFTA3 patients. Furthermore, series biological experiments, including cell viability assays, scratch wound healing colony formation conducted demonstrate tumor-suppressive effects SFTA3. was performed elucidate molecular mechanisms underlying cells. We constructed prognostic model comprising eight genes: ALDOA, ATP5MD, SERPINH1, SFTA3, SLK, U2SURP, SCGB1A1, SCGB1A3. The effectively stratified patients into high- low-risk categories, revealing that experienced superior clinical outcomes, exhibited an immunologically hot tumor microenvironment (TME), had greater probability responding immunotherapy. In contrast, high-risk group cold TME may benefit more from chemotherapy. our study revealed progressive decrease cells correlated advancement. Notably, serum significantly decreased suggesting potential utility liquid biopsy diagnosis. Additionally, knockdown enhances proliferation migration whereas overexpression inhibits these phenotypes. epithelial-mesenchymal transition pathway enriched following silencing, impact by modulating this process. also identified key transcription factors epigenetic implicated downregulation LUAD. developed robust as biomarker applications diagnosis, prognosis, personalized treatment findings offer new insights tumorigenesis immune evasion.

Language: Английский

Citations

0
Analysis of single-cell and spatial transcriptomics in TNBC cell-cell interactions DOI Creative Commons
Yan Xin,

Qiji Ma,

Qiang Deng

et al.

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

Published: Feb. 26, 2025

Triple-negative breast cancer (TNBC) is a highly malignant tumor in women, characterized by high morbidity, mortality, and recurrence rates. Although surgical treatment, radiotherapy, chemotherapy are the mainstays of current treatment methods, heterogeneity TNBC results unsatisfactory outcomes with low 5-year survival Rapid advancements omics technology have propelled understanding molecular biology. The emergence single-cell RNA sequencing (scRNA-seq) spatial transcriptomics (ST) has significantly enhanced knowledge distribution, functionality, intercellular interactions various cell types within microenvironment, including cells, T B macrophages, fibroblasts. present study provides an overview technical characteristics scRNA-seq ST, highlighting their applications exploring heterogeneity, distribution patterns, interactions. This review aims to enhance comprehension at cellular level for development effective therapeutic targets.

Language: Английский

Citations

0
InfoScan: A New Transcript Identification Tool Based on scRNA-Seq and Its Application in Glioblastoma DOI Open Access

Shi-Qiang Mei,

Jinjin Huang, Zhen Zhang

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2208 - 2208

Published: Feb. 28, 2025

InfoScan is a novel bioinformatics tool designed for the comprehensive analysis of full-length single-cell RNA sequencing (scRNA-seq) data. It enables identification unannotated transcripts and rare cell populations, providing powerful platform transcriptome characterization. In this study, was applied to glioblastoma multiforme (GBM), identifying "neoplastic-stemness" subpopulation exhibiting cancer stem cell-like features. Functional analyses suggested that tumor-associated macrophages (TAMs) secrete SPP1, which binds CD44 on neoplastic-stemness cells, activating PI3K/AKT pathway driving lncRNA transcription promote metastasis. Integration TCGA CGGA datasets further supported these findings, highlighting key mutations associated with subpopulation. Drug sensitivity assays indicated cells might be sensitive omipalisib, PI3K inhibitor, pointing potential therapeutic target. offers robust framework exploring complex transcriptomic landscapes characterizing valuable insights into GBM biology advancing precision therapy.

Language: Английский

Citations

0
Decoding the Tumor Microenvironment of Myoepithelial Cells in Triple‐Negative Breast Cancer Through Single‐Cell and Transcriptomic Sequencing and Establishing a Prognostic Model Based on Key Myoepithelial Cell Genes DOI Creative Commons
Xiaocheng Yu, Ye Tian, Rui Zhang

et al.

International Journal of Genomics, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Background: Triple‐negative breast cancer (TNBC) is an aggressive subtype with high malignancy, rapid progression, and a poor 5‐year survival rate of ~77%. Due to the lack targeted therapies, treatment options are limited, highlighting urgent need for novel therapeutic strategies. Myoepithelial cells (MECs) in tumor microenvironment may significantly influence TNBC development progression. Methods: This study used single‐cell RNA sequencing compare MEC gene expression normal versus tissues. TNBC‐associated MECs showed increased proliferation‐ immune‐related genes (e.g., FDCSP, KRT14, KRT17) decreased inflammatory extracellular matrix‐related CXCL8, SRGN, DCN). Copy number variation pseudotime analyses revealed genomic alterations phenotypic dynamics MECs. A CoxBoost‐based prognostic model was developed validated across 20 cohorts, integrating immune profiling, pathway enrichment, drug sensitivity analyses. Mendelian randomization identified TPD52 as risk–associated gene. siRNA knockdown performed cell lines evaluate its effects on proliferation migration. Results: displayed significant changes integrity, impacting responses invasion. The effectively predicted 1‐, 3‐, outcomes, stratifying high‐risk patients enriched cycle DNA replication pathways, reduced checkpoint expression, chemotherapy resistance. tumor‐promoting gene, suppressed Conclusion: highlights MECs’ role provides CoxBoost personalized treatment, identifies potential target intervention.

Language: Английский

Citations

0
SPP1 mRNA Expression Is Associated with M2 Macrophage Infiltration and Poor Prognosis in Triple-Negative Breast Cancer DOI Creative Commons
Yu‐Chia Chen, Chia-Ching Chen, Rong‐Fu Chen

et al.

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(12), P. 13499 - 13513

Published: Nov. 25, 2024

(1): Triple-negative breast cancer (TNBC) is an especially aggressive form of defined by a poor prognosis and lack effective treatment options. There pressing need for validated predictive prognostic biomarkers to assist in making decisions improve the accuracy patients with this challenging disease. (2): We analyzed RNA-seq data from three TNBC tissue samples alongside their corresponding normal tissues. Gene set enrichment analysis (GSEA) identified potential pathways. Additionally, we examined SPP1 mRNA expression datasets available Kaplan–Meier plotter investigated protein patterns our own microarray cohort via immunohistochemistry. (3): The results revealed that genes associated Toll-like receptor signaling pathway showed significant increase activity tissues when compared Furthermore, was found be elevated TCGA dataset correlated prognosis. This pattern corroborated at level cohort; however, did not demonstrate impact on survival. Notably, strongly linked tumor-associated macrophages (TAMs), particularly M2 macrophage subtype, indicating substantial association context TNBC. (4): Our research highlights significance as key indicator molecular responder utilizing targeted therapies focus

Language: Английский

Citations

1
Single-cell Atlas reveals core function of CPVL/MSR1 expressing macrophages in the prognosis of triple-negative breast cancer DOI Creative Commons

Xin’an Wang,

Lin Li, Xue Zhang

et al.

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

Published: Dec. 24, 2024

Background Triple-negative breast cancer (TNBC) is the most aggressive subtype of cancer, with worst prognosis among all subtypes. The impact distinct cell subpopulations within tumor microenvironment (TME) on TNBC patient has yet to be clarified. Methods Utilizing single-cell RNA sequencing (scRNA-seq) integrated bulk (bulk RNA-seq), we applied Cox regression models compute hazard ratios, and cross-validated prognostic scoring using a GLMNET-based model. Cell communication analysis was used elucidate potential mechanisms CPVL MSR1. Ultimately, interference-mediated gene knockdown utilized validate specific genes polarization tumor-associated macrophages (TAMs). Results Our findings revealed that function immune cells more pivotal in prognosis, TAMs showing strongest correlation outcomes, compared other cells. Additionally, identified MSR1 as critical TAMs, expression positively correlated favorable outcomes associated poorer prognosis. Mechanistically, may contribute by inhibiting SPP1-CD44 ligand-receptor promoting CXCL9-CXCR3, C3-C3AR1 ligand-receptor, through which interact such monocytes, neutrophils, T Moreover, cytokines including IL-18, IFNγR1, CCL20, CCL2, along complement-related like TREM2 complement component CFD, participate process or regulating macrophage polarization. Furthermore, RT-PCR experiments confirmed M1-like TAM polarization, while linked M2-like Finally, significance these two also validated HER2-positive Conclusions are biomarkers for macrophage-mediated suggesting therapeutic targeting TNBC.

Language: Английский

Citations

0