Spatial and single‐cell transcriptomic analysis reveals fibroblasts dependent immune environment in colorectal cancer

BioFactors, Journal Year: 2025, Volume and Issue: 51(2)

Published: March 1, 2025

Abstract Colorectal cancer (CRC) exhibits a complex tumor microenvironment with significant cellular heterogeneity, particularly involving cancer‐associated fibroblasts that influence behavior and metastasis. This study integrated single‐cell RNA sequencing spatial transcriptomics to dissect fibroblast heterogeneity in CRC. Data processing employed Seurat for quality control, principal component analysis dimensionality reduction, t‐Distributed Stochastic Neighbor Embedding visualization. Differentially expressed genes were identified using DESeq2. Immune infiltration was assessed via Single‐Sample Gene Set Enrichment Analysis, CIBERSORT, xCell algorithms. Prognostic through univariate Cox regression, followed by consensus clustering survival analysis. Metabolic pathways explored scMetabolism. Experimental validation involved CCK8, scratch, Transwell assays evaluate the roles of key BGN CERCAM CRC cell proliferation Machine learning‐driven four fibroblast‐associated (TRIP6, TIMP1, BGN, CERCAM) demonstrating prognostic relevance Consensus based on these biomarkers stratified patients into three distinct molecular subtypes (Clusters A–C). Notably, Cluster C exhibited most unfavorable clinical outcomes coupled marked upregulation all fibroblast‐related genes. Comprehensive immune profiling revealed paradoxical features C: heightened global activation (characterized substantial leukocyte infiltration) coexisted specific immunosuppressive elements, including enrichment pro‐tumorigenic M0 macrophages, depletion anti‐tumor plasma cells, resting memory CD4+ T along coordinated multiple checkpoint molecules. Computational prediction TIDE platform suggested enhanced immunotherapy responsiveness patients. Functional demonstrated knockdown or significantly impaired malignant phenotypes, reducing proliferative capacity, migration potential, invasive ability. Fibroblasts demonstrate within microenvironment, impacting prognosis therapeutic responses. Key emerge as potential immunotherapeutic targets, offering new strategies precision treatment

Language: Английский

UBE2R2-AS1, as a prognostic marker of gastric cancer, promotes the malignant phenotype of gastric cancer cells.

PubMed, Journal Year: 2024, Volume and Issue: 39(6), P. 739 - 745

Published: June 1, 2024

This study aimed to unveil the potential of UBE2R2-AS1 dysregulation in gastric cancer. In addition, its biological function was assessed.

Language: Английский

Inhibiting the expression of spindle appendix cooled coil protein 1 can suppress tumor cell growth and metastasis and is associated with cancer immune cells in esophageal squamous cell carcinoma

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(8), P. e0302312 - e0302312

Published: Aug. 28, 2024

Inhibiting the expression of spindle appendix cooled coil protein 1 (SPDL1) can slow down disease progression and is related to poor prognosis in patients with esophageal cancer. However, specific roles molecular mechanisms SPDL1 squamous cell carcinoma (ESCC) have not been explored yet. The current study aimed investigate levels ESCC via transcriptome analysis using data from Cancer Genome Atlas (TCGA) Gene Expression Omnibus databases. Moreover, biological roles, mechanisms, networks involved were identified machine learning bioinformatics. counting kit-8 assay, EdU staining, transwell assay used effects inhibiting on proliferation, migration, invasion. Finally, correlation between cancer immune infiltrating cells was evaluated by analyzing TCGA database. Results showed that overexpressed tissues. age ESCC. co-expressed genes included those division, cycle, DNA repair replication, aging, other processes. high-risk scores SPDL1-related long non-coding RNAs significantly correlated overall survival (P < 0.05). effective suppressing invasion TE-1 overexpression positively Th2 T-helper cells, negatively plasmacytoid dendritic mast cells. In conclusion, associated Further, could effectively growth migration. a promising biomarker for treating

Language: Английский