Yu Qi, Shi Xuefeng, Wang Hongjian, Zhang Shun, Hu Songnian, Cai Ting
Department of Experimental Medical Science, Ningbo No.2 Hospital, Ningbo 315010, China.
Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo 315032, China.
J Cancer. 2023 Jul 16;14(12):2209-2223. doi: 10.7150/jca.85873. eCollection 2023.
Hepatocellular carcinoma (HCC) has limited prognostic prediction due to its heterogeneity. Understanding the role of natural killer (NK) cells in HCC is vital for prognosis and immunotherapy guidance. We aimed to identify NK cell marker genes through scRNA-seq and develop a prognostic signature for HCC. We analyzed scRNA-seq data (GSE149614) from 10 patients and bulk RNA-seq data from 786 patients with clinicopathological information. NK cell marker genes were identified using clustering and marker finding functions. A predictive risk signature was constructed using LASSO-COX algorithm. Functional annotations and immune cell infiltration analysis were performed, and the nomogram's performance was evaluated. We identified 79 NK cell marker genes associated with NK cell-mediated cytotoxicity, apoptosis, and immune response. The multigene signature significantly correlated with overall survival (OS) in TCGA-LIHC cohort and was validated in other cohorts. Low-risk patients exhibited higher immune cell infiltration, including CD8 T cells. The risk signature was an independent prognostic factor for OS (HR > 1, < 0.001). The nomogram combining the risk signature and clinical predictors demonstrated robust prognostic ability. We developed a nine-gene signature prognostic model based on NK cell marker genes to accurately assess the prognostic risk of HCC. This model can be a valuable tool for personalized evaluation post-surgery. Our study underscores the potential of NK cells in HCC prognosis and highlights the importance of scRNA-seq analysis in identifying prognostic markers.
由于肝细胞癌（HCC）具有异质性，其预后预测能力有限。了解自然杀伤（NK）细胞在HCC中的作用对于预后和免疫治疗指导至关重要。我们旨在通过单细胞RNA测序（scRNA-seq）鉴定NK细胞标记基因，并开发一种HCC预后特征。我们分析了来自10例患者的scRNA-seq数据（GSE149614）以及来自786例具有临床病理信息患者的批量RNA测序数据。使用聚类和标记发现功能鉴定NK细胞标记基因。使用LASSO-COX算法构建预测风险特征。进行功能注释和免疫细胞浸润分析，并评估列线图的性能。我们鉴定了79个与NK细胞介导的细胞毒性、凋亡和免疫反应相关的NK细胞标记基因。该多基因特征与TCGA-LIHC队列中的总生存期（OS）显著相关，并在其他队列中得到验证。低风险患者表现出更高的免疫细胞浸润，包括CD8 T细胞。风险特征是OS的独立预后因素（HR>1，<0.001）。结合风险特征和临床预测指标的列线图显示出强大的预后能力。我们基于NK细胞标记基因开发了一种九基因特征预后模型，以准确评估HCC的预后风险。该模型可成为术后个性化评估的有价值工具。我们的研究强调了NK细胞在HCC预后中的潜力，并突出了scRNA-seq分析在鉴定预后标志物方面的重要性。
