Qiu Jun, Wang Haoyun, Lv Xin, Mao Lipeng, Huang Junyan, Hao Tao, Li Junliang, Qi Shuo, Chen Guodong, Jiang Haiping
Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou 510630, Guangdong Province, China.
Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of University of South China, Hengyang 421001, Hunan Province, China.
Open Life Sci. 2023 Aug 8;18(1):20220656. doi: 10.1515/biol-2022-0656. eCollection 2023.
The aim of this study is to explore a novel classification and investigate the clinical significance of hepatocellular carcinoma (HCC) cells. We analyzed integrated single-cell RNA sequencing and bulk RNA-seq data obtained from HCC samples. Cell trajectory analysis divided HCC cells into three subgroups with different differentiation states: state 1 was closely related to phosphoric ester hydrolase activity, state 2 was involved in eukaryotic initiation factor 4E binding, translation regulator activity and ribosome, and state 3 was associated with oxidoreductase activity and metabolism. Three molecular classes based on HCC differentiation-related genes (HDRGs) from HCC samples were identified, which revealed immune checkpoint gene expression and overall survival (OS) of HCC patients. Moreover, a prognostic risk scoring (RS) model was generated based on eight HDRGs, and the results showed that the OS of the high-risk group was worse than that of the low-risk group. Further, potential therapeutic drugs were screened out based on eight prognostic RS-HDRGs. This study highlights the importance of HCC cell differentiation in immunotherapy, clinical prognosis, and potential molecular-targeted drugs for HCC patients, and proposes a direction for the development of individualized treatments for HCC.
本研究的目的是探索一种新的分类方法，并研究肝细胞癌（HCC）细胞的临床意义。我们分析了从HCC样本中获得的整合单细胞RNA测序和批量RNA-seq数据。细胞轨迹分析将HCC细胞分为具有不同分化状态的三个亚组：状态1与磷酸酯水解酶活性密切相关，状态2参与真核起始因子4E结合、翻译调节活性和核糖体，状态3与氧化还原酶活性和代谢相关。基于HCC样本中与HCC分化相关基因（HDRGs）确定了三种分子类别，这揭示了HCC患者的免疫检查点基因表达和总生存期（OS）。此外，基于八个HDRGs生成了一个预后风险评分（RS）模型，结果显示高风险组的OS比低风险组更差。进一步地，基于八个预后RS-HDRGs筛选出了潜在的治疗药物。本研究强调了HCC细胞分化在免疫治疗、临床预后以及HCC患者潜在分子靶向药物方面的重要性，并为HCC个体化治疗的发展提出了方向。
