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 and validation of a novel NK cells-related signature to predict prognosis and immune microenvironment in LUAD.
Identification and validation of a novel NK cells-related signature to predict prognosis and immune microenvironment in LUAD.
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肺癌的患病率和致死率正在迅速攀升。自然杀伤(NK)细胞已被证实对肿瘤的发生和进展具有关键作用。然而,其在LUAD预后中的确切意义仍存在不确定性。
数据来源于可靠的数据集,如癌症基因组图谱(TCGA)、基因表达综合数据库(GEO)以及我们内部生成的测序数据。以TCGA数据为背景,我们筛选出交集基因,并通过聚类分析进行验证,进而建立Cox模型,并利用GEO数据集对其进行验证。此外,我们进行了广泛分析,探究潜在生物标志物在免疫细胞浸润、单细胞数据、差异基因表达及药物敏感性方面的意义。
在TCGA数据集中鉴定出67个与NK细胞相关的免疫相关基因(NK-IRGs),其研究潜力通过聚类分析得到证实。利用单因素和多因素Cox模型鉴定出一个预后特征,最终确定了五个基因,并使用GEO数据集进行了验证。此外,列线图的校准曲线显示预测生存率与实际生存率之间具有极好的一致性。后续研究揭示该预后特征可作为独立危险因素。值得注意的是,在低风险组中,NK细胞表现出免疫检查点分子水平升高,表明对免疫治疗具有更高的敏感性。这些发现凸显了利用该特征作为筛选可能从靶向免疫干预中获益的患者的宝贵工具的潜力。
The prevalence and fatality rates of lung cancer are experiencing a rapid escalation. Natural Killer (NK) cells have been established to have a crucial role in both tumor initiation and progression. Nevertheless, uncertainties persist regarding their precise implications in the prognosis of LUAD.
The data were obtained from reputable sources, such as the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) database, and our internally generated sequencing data. Utilizing the TCGA data as a background, we selected intersecting genes, validated by cluster analysis, to establish a Cox model and validated it using the GEO datasets. Furthermore, we conducted extensive analyses to investigate the significance of potential biomarkers in relation to immune cell infiltration, single-cell data, differential gene expression, and drug sensitivity.
67 immune-related genes associated with NK cells (NK-IRGs) were identified in the TCGA datasets, whose research potential was demonstrated by cluster analysis. A prognostic signature was identified utilizing the univariate and multivariate Cox model, resulting in the identification of five genes, which was validated using GEO datasets. Additionally, the nomogram's calibration curve demonstrated exceptional concordance between the projected and actual survival rates. Subsequent investigations uncovered that this prognostic signature demonstrated its independence as a risk factor. Notably, in the low-risk group, NK cells exhibited elevated levels of immune checkpoint molecules, indicating heightened sensitivity to immune therapy. These findings highlight the potential of utilizing this signature as a valuable tool in the selection of patients who could benefit from targeted immune interventions.
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