Chen Nan, Luo Pengyu, Tang Yuna, Liu Pei, Wang Jing, Fan Yuchen, Han Liyan, Wang Kai
Department of Hepatology, Qilu Hospital of Shandong University, Jinan, 250012, People's Republic of China.
Institute of Hepatology, Shandong University, Jinan, 250012, People's Republic of China.
Sci Rep. 2025 Mar 27;15(1):10630. doi: 10.1038/s41598-025-93778-9.
This study investigates the relationship between Cyclin D1 (CCND1) gene and promoter methylation and liver fibrosis (LF)/liver cirrhosis (LC)induced by chronic hepatitis B (CHB). Peripheral blood mononuclear cells (PBMCs) are collected from patients diagnosed with chronic hepatitis B (CHB) and hepatitis B-related LF/LC, as well as from healthy individuals. The mRNA levels and promoter methylation of the CCND1 gene are measured. Single-cell analysis is performed to determine the cell types primarily expressing the CCND1 gene in LF/LC. The GSE84044 dataset is utilized to validate the experimental results. Single-gene GSEA and immune infiltration analyses are conducted to identify significant pathways and immune characteristics associated with the CCND1 gene. The mRNA level of CCND1 in PBMCs from patients with hepatitis B-related LF/LC is elevated compared to those with chronic hepatitis B (CHB) and healthy individuals, while the promoter methylation level of CCND1 is reduced. Single-cell analysis indicates high expression of CCND1 in M2 macrophages (M2) and T cells. The GSE84044 dataset confirms higher CCND1 mRNA levels in liver tissues from patients with CHB-related LF/LC compared to CHB patients. Single-gene GSEA analysis associates CCND1 expression with natural killer cell-mediated cytotoxicity, T cell receptor signaling, and B cell receptor signaling pathways. Increased expression of CCND1 enhances immune infiltration during the fibrosis/cirrhosis process of CHB. The CCND1 expression and promoter methylation may be involved in the process of LF/LC in CHB and may be related to the immune response in the course of the disease.
本研究调查细胞周期蛋白D1（CCND1）基因及其启动子甲基化与慢性乙型肝炎（CHB）所致肝纤维化（LF）/肝硬化（LC）之间的关系。收集诊断为慢性乙型肝炎（CHB）、乙型肝炎相关LF/LC患者以及健康个体的外周血单个核细胞（PBMC）。检测CCND1基因的mRNA水平和启动子甲基化情况。进行单细胞分析以确定在LF/LC中主要表达CCND1基因的细胞类型。利用GSE84044数据集验证实验结果。进行单基因基因集富集分析（GSEA）和免疫浸润分析，以识别与CCND1基因相关的显著通路和免疫特征。与慢性乙型肝炎（CHB）患者和健康个体相比，乙型肝炎相关LF/LC患者PBMC中CCND1的mRNA水平升高，而CCND1的启动子甲基化水平降低。单细胞分析表明，CCND1在M2巨噬细胞（M2）和T细胞中高表达。GSE84044数据集证实，与CHB患者相比，CHB相关LF/LC患者肝组织中CCND1 mRNA水平更高。单基因GSEA分析表明，CCND1表达与自然杀伤细胞介导的细胞毒性、T细胞受体信号通路和B细胞受体信号通路相关。CCND1表达增加会增强CHB纤维化/肝硬化过程中的免疫浸润。CCND1表达和启动子甲基化可能参与CHB患者LF/LC的发生过程，且可能与疾病过程中的免疫反应有关。
