EOGT Correlated With Immune Infiltration: A Candidate Prognostic Biomarker for Hepatocellular Carcinoma

Abstract

BackgroundA preliminary study by our group revealed that the deficiency of EGF domain-specific O-linked N-acetylglucosamine transferase (EOGT) impaired regulatory T-cell differentiation in autoimmune hepatitis. Nevertheless, the prognostic value of EOGT in advanced hepatocellular carcinoma (HCC) and its relationship with immune infiltration remain obscured.MethodsInitially, EOGT expression was evaluated by Oncomine, TIMER, GEO, and UALCAN databases. Besides, the prognostic potential of EOGT expression was analyzed using GEPIA, Kaplan–Meier plotter, CPTAC, Cox regression, and nomogram in HCC samples. Furthermore, we investigated the association between EOGT expression and tumor mutation burden, DNA methylation, and immune infiltration in addition to its possible mechanism via cBioPortal, TIMER, GEPIA, ESTIMATE, CIBERSORT, GSEA, STRING, and Cytoscape.ResultsThe expression of EOGT in HCC was significantly higher than that in normal tissues. Additionally, elevated EOGT expression was correlated with advanced tumor staging and linked to poor overall survival and relapse-free survival, serving as a significant unfavorable prognostic indicator in HCC patients. Remarkably, our results revealed that high-EOGT expression subgroups with elevated TP53 or low CTNNB1 mutations have worse clinical outcomes than the others. Regarding immune infiltration, immunofluorescent staining showed that immune cells in HCC were positive for EOGT. Besides, elevated EOGT expression was linked to exhausted T cells and immune suppressor cells in HCC samples. More importantly, the proportion of CD8+ T cells was reduced in HCC samples with a high level of EOGT expression, but EOGT did not exhibit prognostic potential in HCC samples with increased CD8+ T cells.ConclusionsEOGT may hold great potential as a novel biomarker to distinguish prognosis and immune profiles of HCC patients.

Identification of immune cell-related prognostic genes characterized by a distinct microenvironment in hepatocellular carcinoma

“…Somatic mutations in CTNNB1 were found to antagonize increasing levels of T-cell cytotoxicity or immunological shifts toward cytotoxic CD8+ T cells, leading to the failure of chemotherapy for HCC[ 24 ]. TP53, encoded by the most commonly mutated cancer driver gene, might cooperate with EGF domain-specific O-linked N-acetylglucosamine transferase (EOGT) to reduce the proportion of CD8+ T cells and impair regulatory T-cell differentiation in HCC[ 25 ]. Here, we noticed that the lowest survival probability occurred in patients in the high-risk and high-TMB group, which indicated that that TMB has the potential to serve as a standalone variable in survival analysis, owing to its capacity to modulate immune status.…”

Novel insights into the roles of migrasome in cancer

“…EOGT in Hepatocellular Carcinoma (HCC) correlated with immune infiltration whose expression was significantly higher than that in normal tissues, and it is associated with advanced tumor stage and poor overall survival. Thus, EOGT was considered as a significant poor prognostic indicator for HCC patients[ 100 ]. Generally, EOGT has great promise as a new biomarker, which reflects the progression of pancreatic cancer and HCC.…”

Migrasomes and Tetraspanins in Hepatocellular Carcinoma: Current Status and Future Prospects

“…In the current study, ITGB1 and ITGA5 acted as receptors for the extracellular matrix, and elevated expression of IGTB1 enhances the invasive and proliferative capacity of hepatocellular carcinoma by accelerating the cell cycle process through the PXN/YWHAZ/AKT pathway, whereas ITGA5 was considered to be a prognostic and independent risk factor [ 49 , 50 ]. EOGT is associated with immune infiltration and has the potential to differentiate prognostic markers in patients with hepatocellular carcinoma [ 51 ]. SNP 1048575 was associated with low expression of PIGK in patients with hepatocellular carcinoma [ 52 ].…”