A Novel Prognostic Immune-related Gene Signature in Hepatocellular Carcinoma Through Bioinformatics and Experimental Approaches

Despite therapeutic advancements, treatment failure in hepatocellular carcinoma (HCC) continues to pose a significant obstacle. Given the vital role of the tumor immune microenvironment (TIM) in HCC and the promising effectiveness of immune therapies, we aimed to elucidate potential predictive biomarkers by developing a prognostic model based on immune-related genes (IRGs). After obtaining data, differentially expressed IRGs were identified, and prognostic models were developed using Cox regression analyses. Key contributors of the model were identified and the results were validated by experimental assays in HCC cell lines. Our eight-IRG signature can serve as an independent prognostic factor in HCC. The low-risk group exhibited superior overall survival and lower tumor mutation burden (TMB). The high-risk group showed elevated proportions of immune cells, including regulatory T cells and resting CD4+ memory T cells. We found that the NEAT1-C1/miR-542-5p/BIRC5 regulatory network may serve as a potential target in HCC. The experimental investigations showed that BIRC5 inhibition reduced the metabolic activity in four HCC cell lines. The results of this study facilitate patient stratification and the development of more effective treatment strategies, particularly for high-risk HCC patients.