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基于单细胞分析的自然杀伤(NK)细胞相关基因特征揭示肝细胞癌免疫环境异质性

Natural killer (NK) cells-related gene signature reveals the immune environment heterogeneity in hepatocellular carcinoma based on single cell analysis.

作者信息

Ye Zhirong, Li Wenjun, Ouyang Hao, Ruan Zikang, Liu Xun, Lin Xiaoxia, Chen Xuanting

机构信息

Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Guangdong Medical University, No. 12, Minyou Road, Xiashan District, Zhanjiang, 524000, Guangdong, China.

Department of Anesthesia, Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, 528400, China.

出版信息

Discov Oncol. 2024 Sep 4;15(1):406. doi: 10.1007/s12672-024-01287-4.

DOI:10.1007/s12672-024-01287-4
PMID:39231877
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11374944/
Abstract

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.

摘要

肝癌的早期诊断对于治疗至关重要,且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,使用自然杀伤(NK)细胞相关基因预测模型为基因水平的精准治疗提供依据,并为肝癌患者的治疗提供新的依据。自然杀伤(NK)细胞具有识别和破坏肿瘤细胞的固有能力,因此作为细胞毒性T细胞的“固有对应物”发挥着关键作用。自然杀伤(NK)细胞被公认为是治疗HCC患者肿瘤免疫治疗的一种有前景的方法。在本研究中,我们使用公开可用的数据库收集来自HCC患者的单细胞RNA测序(scRNA-seq)和RNA测序(RNA-seq)的生物信息学数据。为了确定基于自然杀伤(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)细胞并对其进行分析。创建了均匀流形近似和投影图以显示每个标记基因的表达程度和不同簇的分布。进一步分析了免疫治疗反应与基于NKRGs的特征之间的联系,并建立了基于NKRGs的特征。最终,使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。使用基于NKRGs的预后特征可以准确预测HCC的预后,对HCC的NKRGs特征进行全面表征可能有助于解释HCC对免疫治疗的反应,并提出一种新的肿瘤治疗观点。

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本文引用的文献

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Immune checkpoint HLA-E:CD94-NKG2A mediates evasion of circulating tumor cells from NK cell surveillance.免疫检查点 HLA-E:CD94-NKG2A 介导循环肿瘤细胞逃避 NK 细胞监视。
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