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:Natural killer (NK) cells-related gene signature reveals the immune environment heterogeneity in hepatocellular carcinoma based on single cell analysis.
Natural killer (NK) cells-related gene signature reveals the immune environment heterogeneity in hepatocellular carcinoma based on single cell analysis.
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肝癌的早期诊断对治疗至关重要,并依赖于多种检测程序的协同使用。早期诊断对于肝细胞癌(HCC)治疗中的精准治疗至关重要。因此,在本研究中,采用NK细胞相关基因预测模型,为基因层面的精准治疗提供依据,并为肝癌患者的治疗提供新的基础。自然杀伤(NK)细胞具有识别和摧毁肿瘤细胞的先天能力,因此作为细胞毒性T细胞的“先天对应物”发挥着关键功能。自然杀伤(NK)细胞被公认为治疗HCC患者中肿瘤免疫治疗的一种前瞻性方法。
在本研究中,我们利用公开可用的数据库收集了HCC患者的scRNA-seq和RNA-seq的生物信息学数据。为了确定基于NK细胞相关基因(NKRGs)的HCC风险特征,我们分离了T细胞和自然杀伤(NK)细胞并对其进行了分析。创建了均匀流形近似与投影图,以展示各标记基因的表达程度以及不同聚类的分布。
进一步分析了免疫治疗反应与基于NKRGs的特征之间的关系,并建立了基于NKRGs的特征。最终,利用该模型和临床特征开发了一个列线图,以精确预测生存可能性。基于NKRGs的预后特征可以准确预测HCC的预后,而对HCC的NKRGs特征的全面表征可能有助于解读HCC对免疫治疗的反应,并提出一种新的肿瘤治疗视角。
The early diagnosis of liver cancer is crucial for the treatment and depends on the coordinated use of several test procedures. Early diagnosis is crucial for precision therapy in the treatment of the hepatocellular carcinoma (HCC).
Therefore, in this study, the NK cell-related gene prediction model was used to provide the basis for precision therapy at the gene level and a novel basis for the treatment of patients with liver cancer. Natural killer (NK) cells have innate abilities to recognize and destroy tumor cells and thus play a crucial function as the "innate counterpart" of cytotoxic T cells. The natural killer (NK) cells is well recognized as a prospective approach for tumor immunotherapy in treating patients with HCC. In this research, we used publicly available databases to collect bioinformatics data of scRNA-seq and RNA-seq from HCC patients. To determine the NK cell-related genes (NKRGs)-based risk profile for HCC, we isolated T and natural killer (NK) cells and subjected them to analysis.
Uniform Manifold Approximation and Projection plots were created to show the degree of expression of each marker gene and the distribution of distinct clusters. The connection between the immunotherapy response and the NKRGs-based signature was further analyzed, and the NKRGs-based signature was established.
Eventually, a nomogram was developed using the model and clinical features to precisely predict the likelihood of survival. The prognosis of HCC can be accurately predicted using the NKRGs-based prognostic signature, and thorough characterization of the NKRGs signature of HCC may help to interpret the response of HCC to immunotherapy and propose a novel tumor treatment perspective.
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