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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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
背景：乳腺癌（BC）是一种异质性疾病，导管亚型表现出显著的细胞多样性，影响预后和对治疗的反应。本研究利用GEO数据库中的单细胞RNA测序数据来研究细胞异质性的潜在机制，并鉴定潜在的预后标志物和治疗靶标。
方法：使用R包进行生物信息学分析，以分析单细胞测序数据。检查了相同BC样品中高度可变基因的存在和恶性效力的差异。鉴定了1型和2型导管上皮细胞之间的差异基因表达和生物学功能。采用Lasso回归和Cox比例风险回归分析来鉴定与患者预后相关的基因。在体外和体内进行实验验证以确认所鉴定的基因的功能相关性。
结果：分析揭示了BC细胞间的显著异质性，在同一样品中存在高度可变的基因和恶性行为的差异。在1型和2型导管上皮细胞之间发现了基因表达和生物学功能的显着差异。通过回归分析，CYP24A1和TFPI2被鉴定为与患者预后相关的关键基因。Kaplan-Meier曲线证明了它们的预后意义，实验验证证实了它们对导管BC细胞恶性行为的抑制作用。
结论：这项研究强调了导管亚型乳腺癌的细胞异质性，并描述了1型和2型导管上皮细胞之间的差异基因表达和生物学功能。基因CYP24A1和TFPI2成为有希望的预后标志物和治疗靶点，在体外和体内对BC细胞恶性肿瘤表现出抑制作用。这些发现为改善BC管理和制定针对性治疗策略提供了潜力。
方法：使用R包进行生物信息学分析，以分析单细胞测序数据。检查了相同BC样品中高度可变基因的存在和恶性效力的差异。鉴定了1型和2型导管上皮细胞之间的差异基因表达和生物学功能。采用Lasso回归和Cox比例风险回归分析来鉴定与患者预后相关的基因。在体外和体内进行实验验证以确认所鉴定的基因的功能相关性。
结果：分析揭示了BC细胞间的显著异质性，在同一样品中存在高度可变的基因和恶性行为的差异。在1型和2型导管上皮细胞之间发现了基因表达和生物学功能的显着差异。通过回归分析，CYP24A1和TFPI2被鉴定为与患者预后相关的关键基因。Kaplan-Meier曲线证明了它们的预后意义，实验验证证实了它们对导管BC细胞恶性行为的抑制作用。
结论：这项研究强调了导管亚型乳腺癌的细胞异质性，并描述了1型和2型导管上皮细胞之间的差异基因表达和生物学功能。基因CYP24A1和TFPI2成为有希望的预后标志物和治疗靶点，在体外和体内对BC细胞恶性肿瘤表现出抑制作用。这些发现为改善BC管理和制定针对性治疗策略提供了潜力。
