Prognostic and immunotherapeutic predictive value of interleukin enhancer-binding factor 3 in hepatocellular carcinoma: Integrated bioinformatics and experimental analysis

Interleukin enhancer-binding factor 3 (ILF3) as an RNA-binding protein that plays a critical role in the process of cancer and antiviral responses. However, no researcher has focused on the pan-cancer analysis of ILF3, and the effect of ILF3 on tumor immunity is still largely unclear. This study synthetically analyzed the relationship between the expression of ILF3 across various cancers and prognosis, microsatellite instability (MSI), tumor mutational burden (TMB), tumor immune cell infiltration, and common immune checkpoint molecules by multiple bioinformatics databases. Experimentally, we detected the mRNA abundance of ILF3 and immune checkpoint molecules in liver hepatocellular carcinoma (LIHC) tissues. The functions of ILF3 on hepatocellular carcinoma (HCC) cells were verified by western blot assay and cytotoxicity assay. We found that ILF3 was aberrantly expressed and associated with the prognosis in several types of tumors. The ILF3 expression was significantly correlated with infiltrating levels of immune cells and immune molecules in certain cancers, particularly in LIHC. Detection of clinical liver cancer tissues confirmed the positive correlation between ILF3 and immune checkpoint molecules, including programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), cytotoxic T lymphocyte-associated antigen 4 (CTLA4), lymphocyte-activation gene 3 (LAG3), and T cell immunoglobulin domain and mucin domain-3 (TIM3). Furthermore, reduced PD-L1 and increased sensitivity of HCC cells to T cells cytotoxicity were found in ILF3-knockdown cells. This work suggested ILF3 may be used as a prognostic marker for various tumors to predict the response to immunotherapy.