Predictive Roles of ADAM17 in Patient Survival and Immune Cell Infiltration in Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the deadliest malignant tumour worldwide. The metalloproteinase ADAM17 is associated with tumour formation and development; however, its significance in HCC is unclear. This study aimed to investigate the role of ADAM17 in HCC and the correlation between its expression and immune cell infiltration. ADAM17 expression was analysed in pan-cancer and HCC tissues using The Cancer Genome Atlas and Genotype-Tissue Expression datasets. Kaplan–Meier survival analysis displayed a negative association between ADAM17 expression and the overall survival of patients with HCC. High ADAM17 expression was linked to poor tumour/node (T/N) stage and alpha fetoprotein (AFP) levels. Gene Set Enrichment Analysis, Gene Ontology, and Kyoto Encyclopaedia of Genes and Genomes analyses revealed the enrichment of several pathways, including epithelial–mesenchymal transition, inflammatory response, Hedgehog, and KRAS signalling, in patients with upregulated ADAM17. ADAM17 was shown to be positively correlated with immune cell infiltration and immune checkpoint expression via the Tumour Immune Estimation Resource (TIMER) database and immunohistochemistry analyses. Protein–protein interaction (PPI) network analysis revealed that ADAM17 plays a core role in cancer development and immune evasion. In vitro and in vivo experiments demonstrated that ADAM17 influences HCC growth and metastasis. In conclusion, ADAM17 is upregulated in most cancers, particularly HCC, and is critical in the development and immune evasion of HCC.

Keywords

• ADAM17
• hepatocellular carcinoma
• immune cell infiltration
• prognosis
• proliferation
• metastasis