Integrated analysis identifies CD276 in fibroblasts as a malignancy predictor and regulator of neutrophil infiltration in hepatoblastoma

作者：Miao Ding, Guoqing Zhu, Tianshu Chen, Jiabei Zhu, Siwei Mao, Xiaochen Tang, Han Wu, Ni Zhen, Fenyong Sun, Qiuhui Pan, Ji Ma · 发表于：Hepatology Communications · 年份：2025 · DOI：10.1097/hc9.0000000000000826 · 研究领域：Immune cells in cancer、Peptidase Inhibition and Analysis、Neutrophil, Myeloperoxidase and Oxidative Mechanisms

BACKGROUND: Hepatoblastoma is the most prevalent liver cancer in children. Immunotherapy targeting immune checkpoint molecules has become pivotal in various cancer treatments. However, the clinical significance of immune checkpoint ligands in hepatoblastoma remains largely unclear due to various challenges. This study sought to first characterize the expression profile of the immune checkpoint ligand CD276 in hepatoblastoma and assess its potential as a predictor of malignant characteristics and regulator of neutrophil infiltration. METHODS: Univariable and multivariable logistic regression analyses were performed to evaluate the clinical significance of immune checkpoint ligands in the bulk RNA-seq dataset and develop a novel predictive model for malignancy. Furthermore, single-cell RNA sequencing (scRNA-seq), immunohistochemistry (IHC), deconvolution analysis, and correlation analysis were employed to characterize the expression pattern of CD276 and explore its influence on the tumor immune microenvironment. RESULTS: The bulk RNA-seq analysis revealed CD276 transcript levels were significantly elevated in hepatoblastoma tissues, especially in patients with more aggressive malignant phenotypes. Furthermore, we developed a predictive model based on a risk score and constructed a user-friendly nomogram to predict patient metastasis by integrating CD276 levels with clinical features. Both scRNA-seq and multiplex immunohistochemistry (mIHC) analyses confirmed that CD276 is highl...