FZD7 Shapes Mitochondrial Function and Oxidative Stress in Hepatocellular Carcinoma: A Potential Prognostic Biomarker

Mitochondrial metabolism and oxidative stress (OS) play critical roles in the progression of hepatocellular carcinoma (HCC). However, reliable prognostic biomarkers for these processes remain unidentified. This study integrated bulk RNA sequencing and single-cell RNA sequencing (scRNA-seq) to identify OS&mitochondrial metabolism-related genes (OMRGs). A prognostic model was constructed using LASSO regression, followed by external validation. Associations of the model with clinicopathological features, tumor microenvironment (TME), immune functions, therapeutic response, and drug sensitivity were systematically explored. Finally, the relationships between key OMRGs and mitochondrial metabolism as well as OS were validated. A risk score based on five key OMRGs (LPCAT1, IMPDH1, RAMP3, FZD7, and B4GALT5) was established. Low OMRS was significantly associated with improved overall survival and identified as an independent prognostic factor. Two subtypes (C1/C2) were characterized based on the OMRGs: the C1 subtype exhibited poorer survival and epithelial-mesenchymal transition (EMT) enrichment, whereas the C2 subtype showed greater immune infiltration and sensitivity to immunotherapy. High OMRS was associated with higher predicted IC₅₀ values to oxaliplatin and cisplatin, while low OMRS indicated favorable responses to TACE, sorafenib, and immunotherapy. FZD7 knockdown increased reactive oxygen species (ROS) levels and reduced mitochondrial membrane potential in HCC cells. FZD7, a key gene among OMRGs, represent promising prognostic biomarkers and therapeutic targets in HCC.