Distinct Immunophenotypic Profiles and Neutrophil Heterogeneity in Colorectal Cancer

Cancer Letters, Journal Year: 2025, Volume and Issue: 616, P. 217570 - 217570

Published: Feb. 22, 2025

Language: Английский

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Tertiary Lymphoid Structures as a Biomarker in Immunotherapy and Beyond: Advancing Towards Clinical Application

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217491 - 217491

Published: Jan. 1, 2025

Language: Английский

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Identification of Immune Subtypes and a Prognostic Model for Lung Oligometastases in Cervical Cancer

Published: Jan. 1, 2025

Language: Английский

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IL-1β and associated molecules as prognostic biomarkers linked with immune cell infiltration in colorectal cancer: an integrated statistical and machine learning approach

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

Published: Feb. 28, 2025

Abstract Purpose Colorectal cancer (CRC) is the third most common globally, necessitating novel biomarkers for early diagnosis and treatment. This study proposes an efficient pipeline leveraging integrated bioinformatics machine learning framework to enhance identification of diagnostic prognostic CRC. Methods A selection methylated differentially expressed genes (MeDEGs) features (genes) was made using both statistical Machine (ML) approaches from publically available datasets. These were subjected STRING network construction hub estimation, separately. Also, essential miRNAs (micro-RNAs) TFs (Transcription factors) as regulatory elements revealed findings validated through scRNA-seq analysis, promoter methylation, gene expression levels correlated with pathological stage, interaction tumor-infiltrating immune cells. Results Through analysis pipeline, we identified 27 genes, among which CTNNB1, GSK3B, IL-1β, MYC, PXDN, TP53, EGFR, SRC, COL1A1, TGBF1 showed better behaviour. approach includes development K-Nearest Neighbors (KNN), Artificial Neural Networks (ANN), Random Forest (RF) models TCGA datasets, achieving accuracy range between 99 100%. The Area Under Curve (AUC) value each model 1.00, signifying good classification performance. high some associated poor prognosis, concluding IL-1β a biomarker. Additionally, NF-κB microRNAs (miR-548d-3p, miR-548-ac) (NFκB STAT5A) play major role in comprehensive Furthermore, such TGFB1, COL1A1 significantly infiltrates, suggesting their potential CRC progression. Conclusion Overall, elevated coupled abnormal DNA its consequent effect on PI3K/Akt signaling pathway are relevant therapeutic marker Additional molecular candidates reveal insights into epigenetic targets association cell infiltration.

Language: Английский

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Integrative analysis of single-cell and bulk RNA sequencing reveals the oncogenic role of ANXA5 in gastric cancer and its association with drug resistance

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

Published: March 7, 2025

Background Gastric cancer (GC) remains a leading cause of cancer-related mortality, with over one million new cases and 769,000 deaths reported in 2020. Despite advancements chemotherapy, surgery, targeted therapies, delayed diagnosis due to overlooked early symptoms leads poor prognosis. Methods We integrated bulk RNA sequencing single-cell datasets from TCGA, GEO, OMIX001073, employing normalization, batch effect correction, dimensionality reduction methods identify key cell populations associated GC invasion epithelial-mesenchymal transition (EMT), as well analyze the tumor immune microenvironment. Results Our analysis identified MUC5AC+ malignant epithelial cluster significant player EMT. Cluster 1, representing this population, exhibited higher EMT scores compared other clusters. Survival showed that high abundance 0 correlated improved survival rates (P=0.012), whereas 1 was poorer outcomes (P=0.045). A prognostic model highlighted ANXA5 GABARAPL2 two critical genes upregulated tumors. High-risk patients demonstrated increased infiltration worse prognosic. Analysis mutation burden (TMB) indicated low TMB high-risk group had worst Wet-lab validation experiments confirmed oncogenic role ANXA5, showing its facilitation proliferation, invasion, migration while suppressing apoptosis. Conclusion This study offers novel insights into subpopulations cells their roles progression. It provides potential therapeutic targets combat GC, contributing crucial understanding fundamental mechanisms drug resistance gastrointestinal cancers.

Language: Английский

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Tumor organoid-immune co-culture models: exploring a new perspective of tumor immunity

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: April 23, 2025

Abstract Recent advancements in technology have significantly expanded the scope of tumor research, progressing from study individual cells to more intricate tissue and organ-level analyses. Tumor organoids emerged as a highly realistic platform for investigating growth, development, their interactions with surrounding microenvironment. However, notable limitation these is lack diverse cellular composition typically observed actual tumors, which hinders ability fully replicate complexity Immune play pivotal role, immunology has become major research hotspot. Research aims elucidate how immune system recognizes attacks cells, well evade surveillance. In recent years, there been growing interest co-culturing organoids, an approach that yielded valuable insights into between tumors system. The aim this paper review discuss progress achieved cells. By doing so, we hope offer new perspective enhance our understanding diversity inherent

Language: Английский

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Systematic analysis of human colorectal cancer scRNA-seq revealed limited pro-tumoral IL-17 production potential in gamma delta T cells

Neoplasia, Journal Year: 2024, Volume and Issue: 58, P. 101072 - 101072

Published: Oct. 24, 2024

Language: Английский

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Systematic Analysis of Human Colorectal Cancer scRNA-seq Revealed Limited Pro-tumoral IL-17 Production Potential in Gamma Delta T Cells

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 19, 2024

Abstract Gamma delta (γδ) T cells play a crucial role in anti-tumor immunity due to their cytotoxic properties. However, the and extent of γδ production pro-tumorigenic interleukin-17 (IL-17) within tumor microenvironment (TME) colorectal cancer (CRC) remains controversial. In this study, we re-analyzed nine published human CRC whole-tissue single-cell RNA sequencing (scRNA-seq) datasets, identifying 18,483 out 951,785 total cells, neoplastic or adjacent normal tissue 165 patients. Our results confirm that tumor-infiltrating exhibit high cytotoxicity-related transcription both tissues, but critically, none cell clusters showed IL-17 potential. We also identified various subsets, including Teff, TRM, Tpex, Tex, noted an increased expression molecules compared area counterparts. work demonstrates primarily function as effector rather than producers, mitigating concerns about potential roles CRC, highlighting importance accurately characterizing these for immunotherapy research unneglectable cross-species discrepancy between mouse immune system study immunology.

Language: Английский

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Single-cell integration and multi-modal profiling reveals phenotypes and spatial organization of neutrophils in colorectal cancer

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 26, 2024

SUMMARY The immune composition of the tumor microenvironment (TME) has a major impact on therapeutic response and clinical outcome in patients with colorectal cancer (CRC). Here, we comprehensively characterize TME at single-cell level by first building large-scale atlas that integrates 4.27 million single cells from 1,670 patient samples. We then complemented profiles four CRC cohorts 266 patients, including low mRNA content, spatial transcriptional 3.7 cells, protein 0.7 cells. analysis allows refined classification into phenotypes: desert, B cell enriched, T myeloid enriched subtypes. Within compartment uncover distinct subpopulations neutrophils acquire new functional properties blood TME, anti-tumorigenic capabilities. Further, multimodal profiling reveals are organized clusters within niches. Finally, using an orthotopic mouse model show cancer-derived systemic signals modify neutrophil production bone marrow, providing evidence for tumor-induced granulopoiesis. Our study provides big data resource suggests novel strategies targeting neutrophils.

Language: Английский

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Two Decades of Progress in Personalized Medicine of Colorectal Cancer in Serbia—Insights from the Institute for Oncology and Radiology of Serbia

Biomedicines, Journal Year: 2024, Volume and Issue: 12(10), P. 2278 - 2278

Published: Oct. 8, 2024

It is projected that, by 2040, the number of new cases colorectal cancer (CRC) will increase to 3.2 million, and deaths 1.6 highlighting need for prevention strategies, early detection adequate follow-up. In this study, we aimed provide an overview progress in personalized medicine CRC Serbia, with results insights from Institute Oncology Radiology Serbia (IORS), propose guidance tackling observed challenges future.

Language: Английский

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