POFUT1 mRNA expression as an independent prognostic parameter in muscle-invasive bladder cancer

Wahby, Sarah; Jarczyk, Jonas; Fierek, Alexander; Heinkele, Jakob; Weis, Cleo–Aron; Eckstein, Markus; Martini, Thomas; Porubský, Štefan; Hafner, Mathias; Erben, Philipp

doi:10.1016/j.tranon.2020.100900

Cited by 10 publications

(13 citation statements)

References 45 publications

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“…In contrast, low POFUT1 mRNA expression is associated with a higher risk of overall and cancer-specific death in muscle-invasive bladder cancer (MIBC) treated with radical cystectomy. MIBC patients with decreased POFUT1 mRNA levels showed poor outcomes for overall survival, cancerspecific survival, and disease-free survival [126]. In addition to alterations in POFUT1 expression levels, O-fucose site mutations have been detected in anaplastic large cell lymphoma, a type of T-cell lymphoma [133].…”

Section: O-fucosylation Of Notch Receptors In Cancermentioning

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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Section: O-fucosylation Of Notch Receptors In Cancermentioning

confidence: 99%

Significant Roles of Notch O-Glycosylation in Cancer

2022

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“… 32 Wahby et al reported that the expression of poFUT1 was upregulated in bladder cancer, and patients with low poFUT1 level predicted poor overall survival, cancer-specific survival, and disease-free survival, which demonstrated the importance of altered glycosylation for the progress of bladder cancer. 33 FUT7 is a member of the fucosyltransferase family that is known to play a regulatory role in multivariate physiological and pathological processes, such as the formation of endometrial receptivity, 34 embryo implantation, 35 as well as cancer development and metastasis. 36 The overexpression of FUT7 was found in follicular thyroid carcinoma, 25 acute myeloid leukemia, 37 and hepatocarcinoma, 22 etc.…”

Section: Discussionmentioning

confidence: 99%

FUT7 Promotes the Epithelial–Mesenchymal Transition and Immune Infiltration in Bladder Urothelial Carcinoma

Liu¹,

Zheng²,

Chen³

et al. 2021

JIR

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Background Bladder urothelial carcinoma (BLCA) is one of the most frequently appearing, lethal and aggressive malignancies of the genitourinary system with growing morbidity and mortality, which affects human health seriously. Protein glycosylation, catalyzed by specific glycosyltransferase, has been found to be abnormal in several diseases, especially cancer. Fucosyltransferase VII (FUT7), one of the fucosyltransferases, was observed abnormally expressed in various cancers, however, the role of FUT7 in BLCA, and the association between its expression and clinical outcomes or immune infiltration remains unclear. Methodology FUT7 expression in BLCA was analyzed in Oncomine database, which was further confirmed with immunohistochemistry and ELISA. The prognostic value of FUT7 for BLCA was evaluated with PrognoScan database, and its genetic alteration was examined in cBioPortal database. The proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) changes of bladder cancer cells after FUT7 siRNA or cDNA transfection were determined by CCK8, colony formation, transwell and Western blot, respectively. The correlation between FUT7 expression and immune infiltration levels was analyzed in TIMER and TISIDB databases, and the methylation level of FUT7 was detected in UALCAN database. Results The results showed that the expression of FUT7 was increased in BLCA, and patients with high FUT7 level were predicted to have lower overall survival and disease-specific survival rates, which were not influenced by FUT7 genetic alterations. Downregulation FUT7 inhibited the proliferation, migration, invasion and EMT of bladder cancer cells, whereas upregulation of FUT7 showed the opposite effects. We found that FUT7 was positively correlated with immune cell infiltration levels (CD8+ T cells, CD4+T cells, macrophage, neutrophil and dendritic cells), and also the expression of gene markers of immune cells. The negative correlation between FUT7 expression and FUT7 methylation level was observed, among which FUT7 expression was positively correlated with the abundance of 28 kinds of tumor-infiltrating lymphocytes (TILs), while FUT7 methylation level was negatively correlated with TILs. Conclusion Altogether, these findings suggested that FUT7 possessed the potential to serve as a detection biomarker or immunotherapeutic target for BLCA.

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“…A Spearman test was used to analyze the correlation between the expression of different genes. The cut-off values for high and low gene expressions were determined by a partition test with each group representing at least 20% of the total cohort [ 27 , 28 ]. The Kaplan–Meier method and the log-rank test were used for survival analyses and for the Cox regression analysis univariable and multivariable hazard ratios (HR) were used.…”

Section: Methodsmentioning

confidence: 99%

Neuropilin-2 and Its Transcript Variants Correlate with Clinical Outcome in Bladder Cancer

Förster

Givehchi

Nitschke

et al. 2021

Genes

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Urothelial bladder cancer ranks among the 10 most frequently diagnosed cancers worldwide. In our previous study, the transmembrane protein neuropilin-2 (NRP2) emerged as a predictive marker in patients with bladder cancer. NRP2 consists of several splice variants; the most abundant of these, NRP2a and NRP2b, are reported to have different biological functions in lung cancer progression. For other cancer types, there are no published data on the role of these transcript variants in cancer progression and the clinical outcome. Here, we correlate NRP2 and its two most abundant transcript variants, NRP2A and NRP2B, with the clinical outcome using available genomic data with subsequent validation in our own cohort of patients with muscle-invasive bladder cancer. In addition to NRP2, NRP1 and the NRP ligands PDGFC and PDGFD were studied. Only NRP2A emerged as an independent prognostic marker for shorter cancer-specific survival in muscle-invasive bladder cancer in our cohort of 102 patients who underwent radical cystectomy between 2008 and 2014 with a median follow-up time of 82 months. Additionally, we demonstrate that high messenger expression of NRP2, NRP1, PDGFC and PDGFD associates with a more aggressive disease (i.e., a high T stage, positive lymph node status and reduced survival).

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POFUT1 mRNA expression as an independent prognostic parameter in muscle-invasive bladder cancer

Cited by 10 publications

References 45 publications

Significant Roles of Notch O-Glycosylation in Cancer

Significant Roles of Notch O-Glycosylation in Cancer

FUT7 Promotes the Epithelial–Mesenchymal Transition and Immune Infiltration in Bladder Urothelial Carcinoma

Neuropilin-2 and Its Transcript Variants Correlate with Clinical Outcome in Bladder Cancer

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