Construction of PANoptosis-related LncRNA Prognostic Signature and Functional Analysis of AC034229.4 in Hepatocellular Carcinoma

AIMS: This study aimed to establish a PANoptosis related prognostic signature and identify potential prognostic markers and therapeutic targets for HCC. BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The survival rate of patients with HCC remains relatively low. PANoptosis can be mediated by lncRNA to involve the pathophysiology of HCC, but the mechanism is still unclear. OBJECTIVE: TCGA and GEO hepatocellular carcinoma databases and previous research results were used to construct the PANoptosis related risk model. METHODS: Based on the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, this study identified long non-coding RNAs (lncRNAs) associated with PANoptosis in HCC. Univariate, LASSO-Cox, and multivariate COX analyses were employed to gradually screen prognostic lncRNAs and construct prognostic models. Further analysis was conducted on the core lncRNA-AC034229.4. RESULTS: A total of 8 differentially expressed lncRNAs closely correlated with HCC prognosis were discovered. A prognostic model comprising 6 lncRNAs (AC090192.2, LINC01703, AC034229.4, AC073352.1, AC004816.1, and AL136162.1) was established demonstrating good predictive ability for prognosis. Moreover, this prognostic model exhibited close associations with tumor immune microenvironment and immune checkpoints. Subsequent investigations revealed that AC034229.4 independently influenced HCC prognosis by regulating cell cycle progression and inhibiting the immune microenvironment response. Drug sensitivity analysis indicated that AC034229.4 displayed sensitivity to various anticancer drugs as well. In addition, inhibition of AC034229.4 expression suppressed HCC migration and invasion abilities. CONCLUSION: This study generated a novel and efficient prognostic signature model while identifying AC034229.4 as a promising diagnostic and prognostic biomarker in HCC.