E2F1/2/4 mRNA is associated with immune infiltration and are potential biomarkers for the prognosis of human gastric carcinoma

Transl Cancer Res. 2021 Jun;10(6):2801-2811. doi: 10.21037/tcr-21-45.

Abstract

Background: E2Fs are genes that regulate DNA synthesis and the cell cycle by encoding a family of transcription factors. Increasing experimental evidence has revealed that E2Fs play key roles in tumor progression in various types of cancer.

Methods: We investigated the survival, expression and transcriptional data of E2F1/2/4 in gastric cancer (GC) patients using the immunohistochemistry assay, Kaplan-Meier Plotter, cBioPortal, String, and GEPIA databases. The plasma of GC patients was analyzed using the real-time reverse transcription polymerase chain reaction (RT-PCR) assay. The correlation between E2F1/2/4 expression and clinical features was analyzed using the quartile method. As well, the correlation between E2F1/2/4 and GC immune infiltration was also investigated using the TIMER database. Database of Immune Cell Expression (DICE) was also used to analyze correlations between SOX4 and immune responses.

Results: RT-PCR and tissue immunohistochemistry confirmed that E2F1/2/4 was highly expressed in serum and GC tissue samples of GC patients, the expression of which was not affected by patient age and gender. Also, the survival analysis revealed that low levels of E2F1/2/4 expression were significantly associated with a longer overall survival (OS) in GC patients. E2F1/2/4 was correlated with patient prognosis and immune cell infiltration, including B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and DCs in GC. Our findings indicated that E2F1/2/4 could be used as a prognostic biomarker and indicator of immune infiltration in GC.

Conclusions: This study revealed that E2F1/2/4 could be a promising indicator for tumor-associated immune infiltration and prognosis in GC patients.

Keywords: E2F1/2/4; bioinformatics analysis; gastric cancer (GC); immune infiltration.