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

Atieh  Pourbagheri-Sigaroodi; Majid  Momeny; Nima  Rezaei; Fatemeh  Fallah; Davood  Bashash

doi:10.18502/ijaai.v23i6.17380

Atieh Pourbagheri-Sigaroodi Pediatric Infections Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Majid Momeny Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
Nima Rezaei Research Center for Immunodeficiencies, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran
Fatemeh Fallah Pediatric Infections Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Davood Bashash Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/ijaai.v23i6.17380

Keywords: Bioinformatics; BIRC5; Hepatocellular carcinoma; Immune-related signature; Prognostic model; Survivin

Abstract

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.