Identification of a novel ferroptosis-related lncRNA signature for prognostic prediction in hepatocellular carcinoma

Ferroptosis is an iron-dependent form of programmed cell death driven by uncontrolled lipid peroxidation and is widely implicated in cancer progression. Long noncoding RNAs (lncRNAs) serve as critical regulators of ferroptosis; however, their roles in hepatocellular carcinoma (HCC) pathogenesis remain incompletely characterized. This study aimed to preliminarily establish a prognostic model based on ferroptosis-related lncRNAs for HCC. Ferroptosis-related lncRNAs were identified using gene expression and clinical data from The Cancer Genome Atlas (TCGA) database and ferroptosis-related gene sets from FerrDb. A prognostic lncRNA signature was built using Cox regression. Functional enrichment, CIBERSORT, and receiver operating characteristic (ROC) analyses were performed to predict biological functions, characterize immune microenvironment crosstalk, and evaluate signature performance. Drug sensitivity was predicted via OncoPredict. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to detect lncRNA expression in HCC cells. A five ferroptosis-related lncRNA signature could stratify patients into low-risk and high-risk groups with different survival outcomes. High-risk patients were predicted to display altered immune cell infiltration, particularly in macrophages and γδ T cells, and upregulation of oncogenic and proliferative pathways. Drug response predictions indicated potentially enhanced efficacy of 5-fluorouracil, axitinib, bortezomib, paclitaxel, rapamycin, and sorafenib in high-risk patients. RT-qPCR experimental results verified consistent dysregulation of ferroptosis-related lncRNAs in HCC cells versus normal hepatocytes. This study preliminarily elucidated the prognostic significance of a ferroptosis-related lncRNA signature and might offer novel insights into the development of therapeutic strategies for HCC.