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:Integrated single-cell and bulk RNA-seq analysis identifies a prognostic T-cell signature in colorectal cancer.
Integrated single-cell and bulk RNA-seq analysis identifies a prognostic T-cell signature in colorectal cancer.
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结直肠癌(CRC)是全球发病率和死亡率的主要原因,需要更有效的治疗方法。T细胞在肿瘤微环境中占主导地位,在调节CRC的免疫治疗反应和临床结局中发挥关键作用。
本研究引入了一种利用单细胞测序数据表征CRC免疫微环境的开创性方法。与以往聚焦于单个T细胞特征基因的方法不同,我们利用了结直肠癌特征性T细胞的整体浸润水平。通过加权基因共表达网络分析、Lasso回归和StepCox分析,我们基于六个T细胞相关基因开发了一个预后风险模型TRGS(T细胞相关基因特征)。多因素Cox分析确定TRGS是CRC的独立预后因素,其预测效能优于现有的免疫相关预后模型。免疫反应性分析显示,低风险组的Immunophenoscore更高,Tumor Immune Dysfunction and Exclusion评分更低,表明对免疫检查点抑制剂治疗可能具有应答性。
此外,低风险组患者对基于5-氟尿嘧啶的化疗方案表现出更高的敏感性。总之,TRGS作为CRC的独立预后生物标志物,为优化患者对免疫治疗和化疗的应答提供了见解,从而为个性化肿瘤管理策略奠定了基础。
Colorectal cancer (CRC) is a major contributor to global morbidity and mortality, necessitating more effective therapeutic approaches. T cells, prominent in the tumor microenvironment, exert a crucial role in modulating immunotherapeutic responses and clinical outcomes in CRC.
This study introduces a pioneering method for characterizing the CRC immune microenvironment using single-cell sequencing data. Unlike previous approaches, which focused on individual T-cell signature genes, we utilized overall infiltration levels of colorectal cancer signature T-cells. Through weighted gene co-expression network analysis, Lasso regression, and StepCox analysis, we developed a prognostic risk model, TRGS (T-cell related genes signatures), based on six T cell-related genes.
Multivariate Cox analysis identified TRGS as an independent prognostic factor for CRC, showcasing its superior predictive efficacy compared to existing immune-related prognostic models. Immunoreactivity analysis revealed higher Immunophenoscore and lower Tumor Immune Dysfunction and Exclusion scores in the low-risk group, indicating potential responsiveness to immune checkpoint inhibitor therapy.
Additionally, patients in the low-risk group demonstrated heightened sensitivity to 5-fluorouracil-based chemotherapy regimens. In summary, TRGS emerges as a standalone prognostic biomarker for CRC, offering insights to optimize patient responses to immunotherapy and chemotherapy, thereby laying the groundwork for personalized tumor management strategies.
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