MTFR2-dependent mitochondrial fission promotes HCC progression

作者：La Zhang, Xiuzhen Zhang, Haichuan Liu, Changhong Yang, Jiyao Yu, Wei Zhao, Jiao Guo, Baoyong Zhou, N. Jiang · 发表于：Journal of Translational Medicine · 年份：2024 · DOI：10.1186/s12967-023-04845-6 · 被引用次数：51 · 研究领域：Medicine

Background The role of mitochondrial dynamics, encompassing fission, fusion, and mitophagy, in cancer progression has been extensively studied. However, the specific impact of mitochondrial dynamics on hepatocellular carcinoma (HCC) is still under investigation. Methods In this study, mitochondrial dynamic genes were obtained from the MitoCarta 3.0 database, and gene expression data were collected from The Cancer Genome Atlas (TCGA) database. Based on the expression of these dynamic genes and differentially expressed genes (DEGs), patients were stratified into two clusters. Subsequently, a prognostic model was constructed using univariate COX regression and the least absolute shrinkage and selection operator (LASSO) regression, and the prognostic signature was evaluated. We analyzed the interaction between these model genes and dynamic genes to identify hub genes and reveal mitochondrial status. Furthermore, we assessed immune infiltration, tumor mutational burden (TMB), tumor stemness indices (TSI), and the response to immune checkpoint block (ICB) therapy using the TIDE algorithm and risk scores. Additionally, transmission electron microscopy (TEM), hematoxylin-eosin (H&E) staining, immunohistochemistry (IHC), western blotting (WB), and immunofluorescence (IF) were conducted to afford detailed visualization of the morphology of the mitochondria and the expression patterns of fission-associated proteins. Results Patients in Cluster 2 exhibited heightened mitochondrial fissio...