RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Identification of NK cell marker genes based on single-cell sequencing to establish a prognostic signature in breast cancer.
Identification of NK cell marker genes based on single-cell sequencing to establish a prognostic signature in breast cancer.
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我们构建了一个具有强大预测性能的预后特征,阐明了 NK 细胞在乳腺癌发病机制中的关键作用。此外,该模型提供了一个预测指标,并为乳腺癌患者临床管理中免疫治疗策略的发展确定了一个新的治疗靶点。
肿瘤浸润性自然杀伤(NK)细胞在调节肿瘤进展中起关键作用,既可促进也可抑制肿瘤发展。然而,NK 细胞在乳腺癌中的意义仍未被充分了解。本研究旨在阐明 NK 细胞对乳腺癌预后及免疫浸润格局的影响。
利用基因表达综合数据库(GEO)中乳腺癌的单细胞测序数据,鉴定NK细胞标记基因。基于癌症基因组图谱(TCGA)的数据构建预后模型,并随后用GEO数据集进行验证。根据预后模型分层,检查低风险和高风险队列之间免疫细胞浸润的差异。此外,对这两个队列之间差异表达的基因进行富集分析。
通过单细胞测序共鉴定出29个NK细胞标记基因,随后基于TCGA数据利用机器学习技术构建了一个预后模型。该模型在应用于TCGA和GEO数据集时均表现出稳健的预测性能。值得注意的是,低风险组和高风险组之间观察到显著的免疫浸润差异。这些发现通过富集分析得到了进一步验证。
Tumor-infiltrating natural killer (NK) cells are pivotal in modulating tumor progression, either by promoting or inhibiting neoplastic development. Nevertheless, the implications of NK cells in breast carcinoma remain inadequately understood. This investigation aimed to delineate the impact of NK cells on both the prognosis and the immune infiltration landscape in breast cancer.
NK cell marker genes were identified using single-cell sequencing data from breast cancer available in the Gene Expression Omnibus (GEO) database. A prognostic model was constructed based on data from The Cancer Genome Atlas (TCGA) and subsequently validated with the GEO dataset. Disparities in immune cell infiltration between low-risk and high-risk cohorts, as stratified by the prognostic model, were examined. Additionally, genes differentially expressed between these cohorts were subjected to enrichment analysis.
A total of 29 NK cell marker genes were identified through single-cell sequencing, and a prognostic model was subsequently developed using machine learning techniques based on the TCGA data. This model demonstrated robust predictive performance when applied to both TCGA and GEO datasets. Notably, a significant difference in immune infiltration was observed between the low-risk and high-risk groups. The findings were further validated through enrichment analysis.
In summary, we constructed a prognostic signature characterized by strong predictive performance, which has elucidated the critical role of NK cells in the pathogenesis of breast cancer. Furthermore, this model offers a predictive index and identifies a novel therapeutic target for the advancement of immunotherapeutic strategies in the clinical management of breast cancer patients.
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