Fut3 role in breast invasive ductal carcinoma: Investigating its gene promoter and protein expression

Nascimento, Jéssica Catarine Frutuoso do; Ferreira, Steffany de Almeida; Vasconcelos, Juliana Lúcia de Albuquerque; Filho, João Luiz Quirino da Silva; Barbosa, Bruno Trajano; Bezerra, Matheus Filgueira; Rocha, Cecília; Beltrão, Eduardo Isidoro Carneiro

doi:10.1016/j.yexmp.2015.08.015

Cited by 13 publications

(5 citation statements)

References 60 publications

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“…Also, studies have found that higher expression of STXBP6 was favorable for survival in lung adenocarcinoma patients 98 , and STXBP6 overexpression decreased the proliferation and migration of lung adenocarcinoma cells 98 . FUT3 (3-galactosyl-Nacetylglucosaminide 4-alpha-L-fucosyltransferase FUT3) acts as the key enzyme in the synthesis of Lewis antigens closely related to malignant tumors 99 . Genetic polymorphism of FUT3 has been reported to be associated with ulcerative colitis and colon polyps 100,101 .…”

Section: Discussionmentioning

confidence: 99%

Identification of novel protein biomarkers and drug targets for colorectal cancer by integrating human plasma proteome with genome

Sun

Zhao

Jiang

et al. 2022

Preprint

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Background:Proteome is a major source of therapeutic targets. We conducted a proteome-wide Mendelian randomization (MR) study to identify candidate protein markers and therapeutic targets for colorectal cancer (CRC). Methods: Protein quantitative trait loci (pQTL) were derived from seven published genome-wide association studies (GWAS) on plasma proteosome, and summary-level data were extracted for 4,853 circulating protein markers. Genetic associations with CRC were obtained from a large-scaled GWAS meta-analysis (16,871 cases and 26,328 controls), the FinnGen cohort (4,957 cases and 304,197 controls) and the UK Biobank (9,276 cases and 477,069 controls). Colocalization and summary-data-based MR (SMR) analyses were performed sequentially to verify the causal role of candidate proteins. Single cell-type expression analysis, protein-protein interaction (PPI), and druggability evaluation were further conducted to detect the specific cell type with enrichment expression and prioritize potential therapeutic targets. Results: Collectively, genetically predicted levels of 13 proteins were associated with CRC risk. Elevated levels of two proteins (GREM1, CHRDL2) and decreased levels of 11 proteins were associated with an increased risk of CRC, among which six (CLSTN3, POLR2F, ADPGK, CSAG1, STXBP6, FUT3) were novel protein markers. These protein-coding genes mainly expressed in tissue stem cells, epithelial cells, and monocytes in colon tumor tissue. Two interactive pairs of proteins (GREM1 and CHRDL2; MMP2 and TIMP2) were identified to be involved in osteoclast differentiation and tumorigenesis pathways; four proteins (POLR2F, CSF2RA, CD86, MMP2) have been targeted for drug development on autoimmune diseases and other cancers, with the potentials of being repurposed as therapeutic targets for CRC. Conclusion: This study identified several protein biomarkers to be associated with CRC risk and provided new insights into the etiology and promising targets for the development of screening biomarkers and therapeutic drugs for CRC.

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Section: Discussionmentioning

confidence: 99%

Identification of novel protein biomarkers and drug targets for colorectal cancer by integrating human plasma proteome with genome

Sun

Zhao

Jiang

et al. 2022

Preprint

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“…Moreover, in colorectal carcinoma patients, low expression of FUT3 is associated with tumor infiltration and distant metastasis [29]. The dual role of FUT3 in tumor cells suggests that different kinds of tumor modulate FUT3 expression differently to acquire the most beneficial and adaptable characteristics during their establishment in the primary site and later during metastasis [30]. We found that high FUT3 expression was more likely to occur in AML patients with complex karyotype and TP53 mutation, yet its negative prognostic impact on AML was independent, suggesting that FUT3 may also play a positive role in leukemogenesis.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of the FUT family in acute myeloid leukemia

et al. 2019

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Genetic abnormalities are more frequently viewed as prognostic markers in acute myeloid leukemia (AML) in recent years. Fucosylation, catalyzed by fucosyltransferases (FUTs), is a post-translational modification that widely exists in cancer cells. However, the expression and clinical implication of the FUT family (FUT1-11) in AML has not been investigated. From the Cancer Genome Atlas database, a total of 155 AML patients with complete clinical characteristics and FUT1-11 expression data were included in our study. In patients who received chemotherapy alone showed that high expression levels of FUT3, FUT6, and FUT7 had adverse effects on event-free survival (EFS) and overall survival (OS) (all P < 0.05), whereas high FUT4 expression had favorable effects on EFS and OS (all P < 0.01). However, in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) group, we only found a significant difference in EFS between the high and low FUT3 expression subgroups (P = 0.047), while other FUT members had no effect on survival. Multivariate analysis confirmed that high FUT4 expression was an independent favorable prognostic factor for both EFS (HR = 0.423, P = 0.001) and OS (HR = 0.398, P < 0.001), whereas high FUT6 expression was an independent risk factor for both EFS (HR = 1.871, P = 0.017) and OS (HR = 1.729, P = 0.028) in patients who received chemotherapy alone. Moreover, we found that patients with low FUT4 and high FUT6 expressions had the shortest EFS and OS (P < 0.05). Our study suggests that high expressions of FUT3/6/7 predict poor prognosis, high FUT4 expression indicates good prognosis in AML; FUT6 and FUT4 have the best prognosticating profile among them, but their effects could be neutralized by allo-HSCT.

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“…However, FUT3 (Fucosyltransferase 3) is involved in embryogenesis, tissue differentiation, tumor metastasiss and inflammation. Incidences of gastro-intestinal and breast cancer are linked to FUT3 genetic variations ( 43 , 44 ). Similarly, we also discovered rs151218854 in FUT3 related to incidence of CML.…”

Section: Discussionmentioning

confidence: 99%

Identification of prognostic and susceptibility markers in chronic myeloid leukemia using next generation sequencing

Shokeen¹,

Sharma²,

Vats³

et al. 2018

Ethiop J Health Sci

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BackgroundIncidence of Chronic Myeloid Leukemia (CML) is continuously increasing and expected to reach 100,000 patients every year by 2030. Though the discovery of Imatinib Mesylate (IM) has brought a paradigm shift in CML treatment, 20% patients show resistance to this tyrosine kinase inhibiter (TKI). Therefore, it is important to identify markers, which can predict the occurrence and prognosis of CML. Clinical Exome Sequencing, panel of more than 4800 genes, was performed in CML patients to identify prognostic and susceptibility markers in CML.MethodsEnrolled CML patients (n=18) were segregated as IM responders (n=10) and IM failures (n=8) as per European Leukemia Net (ELN), 2013 guidelines. Healthy controls (n=5) were also enrolled. DNA from blood of subjects was subjected to Next Generation Sequencing. Rare mutations present in one patient group and absent in another group were considered as prognostic markers, whereas mutations present in more than 50% patients were considered as susceptibility markers.ResultMutations in genes associated with cancer related functions were found in different patient groups. Four variants: rs116201358, rs4014596, rs52897880 and rs2274329 in C8A, UNC93B1, APOH and CA6 genes, respectively, were present in IM responders; whereas rs4945 in MFGE8 was present in IM failures. Mutations in HLA-DRB1 (rs17878951), HLA-DRB5 (rs137863146), RPHN2 (rs193179333), CYP2F1 (rs116958555), KCNJ12 (rs76684759) and FUT3 (rs151218854) were present as susceptibility markers.ConclusionThe potential genetic markers discovered in this study can help in predicting response to IM as frontline therapy. Susceptibility markers may also be used as panel for individuals prone to have CML.

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Fut3 role in breast invasive ductal carcinoma: Investigating its gene promoter and protein expression

Cited by 13 publications

References 60 publications

Identification of novel protein biomarkers and drug targets for colorectal cancer by integrating human plasma proteome with genome

Identification of novel protein biomarkers and drug targets for colorectal cancer by integrating human plasma proteome with genome

Prognostic value of the FUT family in acute myeloid leukemia

Identification of prognostic and susceptibility markers in chronic myeloid leukemia using next generation sequencing

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