Bioinformatics and Functional Analyses Implicate Potential Roles for EOGT and L-fringe in Pancreatic Cancers

Barua, Rashu; Mizuno, Kazuyuki; Tashima, Yohtalou; Ogawa, Masamichi; Takeuchi, Hideyuki; Taguchi, Ayumu; Okajima, Tetsuya

doi:10.3390/molecules26040882

Cited by 23 publications

(12 citation statements)

References 53 publications

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“…First of all, our pan-cancer analysis showed that EOGT was highly expressed in five types of cancer, namely, CHOL, HNSC, KIRC, HCC, and THCA. However, there were studies that showed that EOGT expression was increased in PAAD ( 9 , 10 ), which contradicted with our results, because they did not consider the classical subtype of PAAD. Results from GEO and Oncomine consistently demonstrated that EOGT expression was obviously elevated in HCC samples.…”

Section: Discussioncontrasting

confidence: 99%

“…Notably, KM survival analysis using the KM plotter and CPTAC further proved that elevated EOGT expression was closely linked to poor OS and RFS in HCC samples. Moreover, it was reported that low expression of both EOGT and LFNG was associated with favorable OS in pancreatic ductal adenocarcinoma patients ( 9 ). In a recent study, IHC staining in sequencing samples confirmed that EOGT was linked to poor OS in pancreatic cancer ( 10 ).…”

Section: Discussionmentioning

confidence: 99%

“…A previous research by our group demonstrated that in EOGT -deficient rats, regulatory T-cell (Treg) differentiation was dramatically impaired because of inactivation of Notch signaling, giving rise to abnormal T-cell infiltration into the liver ( 8 ). Recently, it was reported that dysregulated Notch signaling mediated by EOGT and lunatic fringe correlated with unfavorable prognosis in pancreatic ductal adenocarcinoma patients ( 9 ). Meanwhile, studies had also indicated that Shc SH2-domain-binding protein 1 and EOGT were involved in the progression of pancreatic cancer, promoting O-GlcNAcylation of NOTCH1 ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

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

Yang

Gao

et al. 2022

Front. Immunol.

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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.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Yang

Gao

et al. 2022

Front. Immunol.

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“…The abnormal expression of Notch receptors, ligands, and their downstream target genes in pancreatic ductal adenocarcinoma (PDAC) suggests that Notch signaling plays a role in the development and progression of pancreatic tumors [ 149 , 150 , 151 ]. O -GlcNAcylation also plays an important role in PDAC development [ 152 ]. The expression levels of EOGT and Shc SH2-binding protein 1 (SHCBP1) were significantly increased in patients with PDAC, which was associated with a worse prognosis.…”

Section: Significance Of Notch O -Glycosylation In...mentioning

confidence: 99%

Significant Roles of Notch O-Glycosylation in Cancer

2022

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Notch signaling, which was initially identified in Drosophila wing morphogenesis, plays pivotal roles in cell development and differentiation. Optimal Notch pathway activity is essential for normal development and dysregulation of Notch signaling leads to various human diseases, including many types of cancers. In hematopoietic cancers, such as T-cell acute lymphoblastic leukemia, Notch plays an oncogenic role, while in acute myeloid leukemia, it has a tumor-suppressive role. In solid tumors, such as hepatocellular carcinoma and medulloblastoma, Notch may have either an oncogenic or tumor-suppressive role, depending on the context. Aberrant expression of Notch receptors or ligands can alter the ligand-dependent Notch signaling and changes in trafficking can lead to ligand-independent signaling. Defects in any of the two signaling pathways can lead to tumorigenesis and tumor progression. Strikingly, O-glycosylation is one such process that modulates ligand–receptor binding and trafficking. Three types of O-linked modifications on the extracellular epidermal growth factor-like (EGF) repeats of Notch receptors are observed, namely O-glucosylation, O-fucosylation, and O-N-acetylglucosamine (GlcNAc) modifications. In addition, O-GalNAc mucin-type O-glycosylation outside the EGF repeats also appears to occur in Notch receptors. In this review, we first briefly summarize the basics of Notch signaling, describe the latest information on O-glycosylation of Notch receptors classified on a structural basis, and finally describe the regulation of Notch signaling by O-glycosylation in cancer.

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“…Barua et al reported that the O-GlcNAcylation of Notch receptor participated in the regulation of proliferation and migration of Panc-1 pancreatic cancer cells. 35 Stateva and Villalobo reported the presence of O-GlcNAcylated EGFR in the A431 skin squamous and the A549 lung cancer cell lines. 5 Moreover, Wang et al observed that knockdown of OGT in the 786-O kidney cancer cell line led to a downregulation of EGFR O-GlcNAcylation.…”

Section: Potential Applications Of the Nanotechnique For Targeting O-...mentioning

confidence: 99%

How Nanotechniques Could Vitalize the O-GlcNAcylation-Targeting Approach for Cancer Therapy

Yang¹,

Wang²,

Wu³

et al. 2022

IJN

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Bioinformatics and Functional Analyses Implicate Potential Roles for EOGT and L-fringe in Pancreatic Cancers

Cited by 23 publications

References 53 publications

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

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

Significant Roles of Notch O-Glycosylation in Cancer

How Nanotechniques Could Vitalize the O-GlcNAcylation-Targeting Approach for Cancer Therapy

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