Background: E2F1 is an important transcription factor. Previous studies have shown that the overexpression of E2F1 is closely related to the occurrence and development of hepatocellular carcinoma (HCC). However, the current research on the regulatory mechanism of E2F1 is still insufficient. This study sought to identify valuable therapeutic E2F1-related targets for HCC.
Methods: HCC-related transcriptome data and patient clinical information downloaded from The Cancer Genome Atlas (TCGA) database. The expression of the E2F1 gene in pan-cancer was analyzed using the Tumor IMmune Estimation Resource (TIMER) 2.0 database, and the expression level of E2F1 in HCC was verified using the Gene Expression Profiling Interactive Analysis database. The overall survival (OS) and progression-free survival (PFS) in HCC patients were also analyzed. Subsequently, based on the Encyclopedia of RNA Interactomes (ENCORI) database, we adopted E2F1 as the research objective and identified the target long non-coding RNAs (lncRNAs) and microRNAs that suggested the competing endogenous RNA (ceRNA) mechanisms related to E2F1. We also performed a correlation analysis of E2F1 using the R language package that contained immune cell and immune checkpoint information. Finally, the drug sensitivity of E2F1 was detected using the R language package, "pRRophetic."
Results: Ultimately, the following 6 potential ceRNA-based pathways targeting E2F1 were identified-lncRNA: LINC01224, PCBP1-AS1, and ITGA9-AS1-miR-29b-3p-E2F1; lncRNA: SNHG7 and THUMPD3-AS1, and LINC02323-miR-29c-3p-E2F1. Cluster of differentiation (CD)4 memory activated T cells, memory B cells, eosinophils, and T follicular helper cells were positively correlated with E2F1 (P<0.05), and monocytes, naïve B cells, and CD4 memory resting T cells were negatively correlated with E2F1 (P<0.05). The immune checkpoint analysis showed that E2F1 was positively correlated with PDCD1, CTLA4, and LAG3 (P>0.2). According to the drug sensitivity analysis, E2F1 may be sensitive to 39 drugs (P<0.05).
Conclusions: This study provides a valuable direction for researching transcription factor E2F1, which may be conducive in identifying research targets for HCC-related molecular biological therapy and immunotherapy in future.
Keywords: Competing endogenous RNA (ceRNA); E2F1; bioinformatics; hepatocellular carcinoma (HCC); immunoassay.
2022 Journal of Gastrointestinal Oncology. All rights reserved.