ArticleFrontiers in oncology2025
Integrating single-cell transcriptomics and whole-genome CRISPR CAS9 screen identifies a cell cluster associated with tumor dependency in triple-negative breast cancer.
Article in Frontiers in oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Comprehensive profiling of RPP40 across human cancers reveals its essential role and multidimensional clinical correlates.Discover oncology · 2026Article
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7 authors.
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Abstract
Background: Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype; however, clinically approved prognostic biomarkers and therapeutic options remain limited. This study aimed to investigate tumor dependency genes to identify novel therapeutic targets for TNBC. Methods: Tumor dependency genes for TNBC were identified using the The Cancer Dependency Map (DEPMAP) database. The TCGA-BRCA dataset was utilized to analyze the expression, survival associations, and pathway enrichment of these genes. Single-cell datasets were employed to explore cellular trajectories and biological functions within tumor dependency gene-associated cell subpopulations. Genomic sequencing was used to investigate the somatic mutational landscape influencing the infiltration abundance of the tumor dependency-associated subpopulation. The METABRIC dataset assessed the impact of the tumor dependency-associated subpopulation on radiotherapy, chemotherapy, and combination therapy outcomes. Potential drugs were identified using the Connectivity Map (CMAP). Colony formation experiment and the CCK-8 experiment were performed to validate the biological function of gene. Results: Four tumor dependency genes (TDGs) were identified. These genes were highly expressed in TNBC and associated with poor prognosis. Enrichment analysis revealed their significant involvement in cell cycle-related pathways. Single-cell analysis demonstrated that the tumor dependency-associated subpopulation (TDAS), defined by these four genes, resided at the differentiation terminus of epithelial/tumor cells and was linked to energy metabolism and cell proliferation pathways. Crucially, patients with high TDAS infiltration abundance were found to be unsuitable for surgery alone and should receive combined radiotherapy or chemotherapy. Potential therapeutic agents targeting the TDAS were screened. And Conclusion: This study identifies four potential TNBC biomarkers for assessing TDAS abundance, providing novel insights and strategies for personalized TNBC treatment.
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