Zhu Qian, Xie Yuwei, Qiu Kang, Wu Tingting, Hao Xiwei, Zhu Chengzhan
Department of Pediatric Surgery, The Affiliated Hospital of Qingdao University, No.16 Jiangsu Road,266003 Qingdao, People's Republic of China.
Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, No.16 Jiangsu Road,266003 Qingdao, People's Republic of China.
Gene. 2025 Jun 9;964:149604. doi: 10.1016/j.gene.2025.149604.
Hepatoblastoma is a common tumor in childhood, characterized by immature histology and diverse cell lineages. The purpose of this study is to identify the genes that are abnormally expressed in hepatoblastoma, and to explore the targets of intercellular communication that affect the tumor immune microenvironment.
Through comprehensive analysis of gene expression from GSE133039 and GSE180664 data sets, the differentially expressed genes in cancer tissues and adjacent tissues were obtained. GO and KEGG enrichment analysis is used to predict the biological function and signal transduction pathway of differential expression gene enrichment. Use cytoscape to build PPI network to filter hubgene; Construct correlation analysis of immune cell infiltration to infer the correlation between immune cells. Combined with single-cell transcriptome data, further reveal the relationship between cells and signal targets of cell communication. The effects of LFNG expression on migration and invasion were assessed through Scratch wound‑healing assay and Transwell assays in HUH6 cells.
58 differentially expressed genes with high expression and 94 differentially expressed genes with low expression were obtained from the two data sets of hepatoblastoma. They were mainly involved in the signal transduction related to metastasis. PPI network screened 50 hubgenes. The correlation analysis of immune cell infiltration of different genes showed that macrophages were significantly correlated with endothelial cells. Combined with the analysis of single-cell transcriptome data, hepatoblastoma was divided into 11 cell subpopulations, and 16 genes in hubgene were expressed in different cell subpopulations, in which LFNG was highly expressed in macrophages and monocytes, which served as the target of intercellular communication to promote the development of hepatoblastoma. The biological function experiments validates the role of LFNG overexpression in migration and invasion of the hepatoblastoma cells.
In this study, we identified the genes that were abnormally expressed in hepatoblastoma, and affected the cellular communication of hepatoblastoma through LFNG target, thus affecting the progress of tumor. LFNG overexpression promoted tumor invasion and migration. Therefore, LFNG may become a therapeutic target for hepatoblastoma.
肝母细胞瘤是儿童期常见肿瘤，具有不成熟的组织学特征和多样的细胞谱系。本研究旨在鉴定在肝母细胞瘤中异常表达的基因，并探索影响肿瘤免疫微环境的细胞间通讯靶点。
通过对GSE133039和GSE180664数据集的基因表达进行综合分析，获得癌组织和癌旁组织中的差异表达基因。采用GO和KEGG富集分析预测差异表达基因富集的生物学功能和信号转导途径。利用Cytoscape构建PPI网络以筛选枢纽基因；构建免疫细胞浸润的相关性分析以推断免疫细胞之间的相关性。结合单细胞转录组数据，进一步揭示细胞与细胞通讯的信号靶点之间的关系。通过划痕伤口愈合试验和Transwell试验评估LFNG表达对HUH6细胞迁移和侵袭的影响。
从肝母细胞瘤的两个数据集中获得了58个高表达差异表达基因和94个低表达差异表达基因。它们主要参与与转移相关的信号转导。PPI网络筛选出50个枢纽基因。不同基因的免疫细胞浸润相关性分析表明，巨噬细胞与内皮细胞显著相关。结合单细胞转录组数据分析，将肝母细胞瘤分为11个细胞亚群，枢纽基因中的16个基因在不同细胞亚群中表达，其中LFNG在巨噬细胞和单核细胞中高表达，作为细胞间通讯的靶点促进肝母细胞瘤的发展。生物学功能实验验证了LFNG过表达在肝母细胞瘤细胞迁移和侵袭中的作用。
在本研究中，我们鉴定了在肝母细胞瘤中异常表达的基因，并通过LFNG靶点影响肝母细胞瘤的细胞通讯，从而影响肿瘤进展。LFNG过表达促进肿瘤侵袭和迁移。因此，LFNG可能成为肝母细胞瘤的治疗靶点。
