AI Article Synopsis
- Breast cancer (BC), particularly the ductal subtype, shows significant cellular diversity which affects treatment outcomes; this study uses single-cell RNA sequencing data to explore this heterogeneity and identify potential markers for prognosis and therapy.
- Bioinformatics methods were applied to analyze single-cell sequencing data, highlighting differences in gene expression and behavior between Type 1 and Type 2 ductal epithelial cells, along with identifying key genes (CYP24A1 and TFPI2) linked to patient prognosis.
- The findings underscore the importance of cellular heterogeneity in ductal BC, revealing CYP24A1 and TFPI2 as significant prognostic markers and therapeutic targets, with validation showing their role in inhibiting malignant behaviors in BC cells.
Article Abstract
Background: Breast cancer (BC) is a heterogeneous disease, with the ductal subtype exhibiting significant cellular diversity that influences prognosis and response to treatment. Single-cell RNA sequencing data from the GEO database were utilized in this study to investigate the underlying mechanisms of cellular heterogeneity and to identify potential prognostic markers and therapeutic targets.
Methods: Bioinformatics analysis was conducted using R packages to analyze the single-cell sequencing data. The presence of highly variable genes and differences in malignant potency within the same BC samples were examined. Differential gene expression and biological function between Type 1 and Type 2 ductal epithelial cells were identified. Lasso regression and Cox proportional hazards regression analyses were employed to identify genes associated with patient prognosis. Experimental validation was performed in vitro and in vivo to confirm the functional relevance of the identified genes.
Results: The analysis revealed notable heterogeneity among BC cells, with the presence of highly variable genes and differences in malignant behavior within the same samples. Significant disparities in gene expression and biological function were identified between Type 1 and Type 2 ductal epithelial cells. Through regression analyses, CYP24A1 and TFPI2 were identified as pivotal genes associated with patient prognosis. Kaplan-Meier curves demonstrated their prognostic significance, and experimental validation confirmed their inhibitory effects on malignant behaviors of ductal BC cells.
Conclusion: This study highlights the cellular heterogeneity in ductal subtype breast cancer and delineates the differential gene expressions and biological functions between Type 1 and Type 2 ductal epithelial cells. The genes CYP24A1 and TFPI2 emerged as promising prognostic markers and therapeutic targets, exhibiting inhibitory effects on BC cell malignancy in vitro and in vivo. These findings offer the potential for improved BC management and the development of targeted treatment strategies.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11282761 | PMC |
| http://dx.doi.org/10.1186/s12935-024-03325-1 | DOI Listing |
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