He Zhaobin, Peng Cheng, Li Tianen, Li Jie
Department of Hepatobiliary Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Department of Hepatobiliary Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Front Genet. 2022 Mar 10;13:858905. doi: 10.3389/fgene.2022.858905. eCollection 2022.
Most hepatocellular carcinoma (HCC) patients occur on a background of liver cirrhosis, the molecular mechanisms of liver cirrhosis and its progression to HCC remain to be fully elucidated. Single cell differentiation trajectory analysis has been used in cell classification and tumor molecular typing, which correlated with disease progression and patient prognosis. Here we use cell differentiation trajectory analysis to investigate the relevance of liver cirrhosis and HCC. Single-cell RNA sequencing (scRNA-seq) data of liver cirrhosis and bulk RNA-seq and clinical data of HCC were downloaded from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) for analysis. HCC samples were divided into three subtypes, based on differentiation-related genes (DRGs) of liver cirrhosis, each with a different expression profile and overall survival (OS). A two- DRGs (CD34 and RAMP3) based prognostic risk scoring (RS) signature was established which could differentiate OS between high-risk and low-risk groups. And expression levels of CD34 and RAMP3 were predominantly high in endothelial cells. By integrating the RS and clinicopathological features, a nomogram was constructed and can accurately predicted the 1-year, 3-years, and 5-years OS. In conclusion, cell differentiation trajectory of liver cirrhosis can predict the prognosis of HCC, and provides new perspectives on the mechanisms of progression of liver cirrhosis to HCC.
大多数肝细胞癌（HCC）患者发生在肝硬化背景下，肝硬化及其进展为HCC的分子机制仍有待充分阐明。单细胞分化轨迹分析已用于细胞分类和肿瘤分子分型，其与疾病进展和患者预后相关。在此，我们使用细胞分化轨迹分析来研究肝硬化与HCC的相关性。从基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）下载肝硬化的单细胞RNA测序（scRNA-seq）数据、HCC的批量RNA-seq数据和临床数据进行分析。基于肝硬化的分化相关基因（DRG），将HCC样本分为三个亚型，每个亚型具有不同的表达谱和总生存期（OS）。建立了基于两个DRG（CD34和RAMP3）的预后风险评分（RS）特征，其可以区分高风险组和低风险组的OS。并且CD34和RAMP3的表达水平在内皮细胞中主要较高。通过整合RS和临床病理特征，构建了列线图，其可以准确预测1年、3年和5年的OS。总之，肝硬化的细胞分化轨迹可以预测HCC的预后，并为肝硬化进展为HCC的机制提供新的视角。
