ArticleFrontiers in immunology2024
Comprehensive single-cell and bulk transcriptomic analyses to develop an NK cell-derived gene signature for prognostic assessment and precision medicine in breast cancer.
Article in Frontiers in immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Anticancer Potential of Cherry Extracts and Major Flavonols: Focus on Quercetin and Kaempferol Molecular Mechanisms in Breast Cancer.International journal of molecular sciences · 2026Review
- Perioperative Changes in Peripheral Natural Killer Cell Activity and Their Association With Clinicopathological Features in Breast Cancer: A Single-Center Cohort Study.Cancer medicine · 2026Article
- KLRB1 gene in tumor immune regulation and disease prognosis: a multidimensional role review.Discover oncology · 2026Review
- Bioinformatic Analysis of Contrasting Expression Patterns and Molecular Interactions of TIMPs in Breast Cancer: Implications for Tumor Progression and Survival.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Article
- Identification of NK cell marker genes based on single-cell sequencing to establish a prognostic signature in breast cancer.Discover oncology · 2025Article
- SOCS3: An Immunological Biomarker Offering Potential Therapeutic Targets for Malignant Tumors.Biological procedures online · 2025Review
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Authors and funding
8 authors.
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Abstract
Background: Natural killer (NK) cells play crucial roles in mediating anti-cancer activity in breast cancer (BRCA). However, the potential of NK cell-related molecules in predicting BRCA outcomes and guiding personalized therapy remains largely unexplored. This study focused on developing a prognostic and therapeutic prediction model for BRCA by incorporating NK cell-related genes. Methods: The data analyzed primarily originated from the TCGA and GEO databases. The prognostic role of NK cells was evaluated, and marker genes of NK cells were identified via single-cell analysis. Module genes closely associated with immunotherapy resistance were identified by bulk transcriptome-based weighted correlation network analysis (WGCNA). Following taking intersection and LASSO regression, NK-related genes (NKRGs) relevant to BRCA prognosis were screened, and the NK-related prognostic signature was subsequently constructed. Analyses were further expanded to clinicopathological relevance, GSEA, tumor microenvironment (TME) analysis, immune function, immunotherapy responsiveness, and chemotherapeutics. Key NKRGs were screened by machine learning and validated by spatial transcriptomics (ST) and immunohistochemistry (IHC). Results: Tumor-infiltrating NK cells are a favorable prognostic factor in BRCA. By combining scRNA-seq and bulk transcriptomic analyses, we identified 7 NK-related prognostic NKRGs (CCL5, EFHD2, KLRB1, C1S, SOCS3, IRF1, and CCND2) and developed an NK-related risk scoring (NKRS) system. The prognostic reliability of NKRS was verified through survival and clinical relevance analyses across multiple cohorts. NKRS also demonstrated robust predictive power in various aspects, including TME landscape, immune functions, immunotherapy responses, and chemotherapeutic sensitivity. Additionally, KLRB1 and CCND2 emerged as key prognostic NKRGs identified through machine learning and external validation, with their expression correlation with NK cells confirmed in BRCA specimens by ST and IHC. Conclusions: We developed a novel NK-related gene signature that has proven valuable for evaluating prognosis and treatment response in BRCA, expecting to advance precision medicine of BRCA.
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