Deciphering hepatocellular carcinoma pathogenesis and therapeutics: a study on anoikis, ceRNA regulatory network and traditional Chinese medicine

Abstract

Introduction: Hepatocellular carcinoma (HCC) is responsible for approximately 90% of liver malignancies and is the third most common cause of cancer-related mortality worldwide. However, the role of anoikis, a programmed cell death mechanism crucial for maintaining tissue equilibrium, is not yet fully understood in the context of HCC. Methods: Our study aimed to investigate the expression of 10 anoikis-related genes (ARGs) in HCC, including BIRC5, SFN, UBE2C, SPP1, E2F1, etc., and their significance in the disease. Results: Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, we discovered that these ARGs are involved in important processes such as tissue homeostasis, ion transport, cell cycle regulation, and viral infection pathways. Furthermore, we found a significant correlation between the prognostic value of five ARGs and immune cell infiltrates. Analysis of clinical datasets revealed a strong association between BIRC5 expression and HCC pathological progression, including pathological stage, T stage, overall survival (OS), and race. By constructing a competing endogenous RNA (ceRNA) network and using molecular docking, we identified ten bioactive compounds from traditional Chinese medicine (TCM) that could potentially modulate BIRC5. Subsequent in vitro experiments confirmed the influence of platycodin D, one of the identified compounds, on key elements within the ceRNA network. Discussion: In conclusion, our study presents a novel framework for an anoikis-centered prognostic model and an immune-involved ceRNA network in HCC, revealing potential regulatory targets. These insights contribute to our understanding of HCC pathology and may lead to improved therapeutic interventions.