Reduced expression of α-L-Fucosidase-1 (FUCA-1) predicts recurrence and shorter cancer specific survival in luminal B LN+ breast cancer patients

Bonin, Serena; Parascandolo, Alessia; Aversa, Cinzia; Barbazza, Renzo; Tsuchida, Nobuo; Castellone, Maria Domenica; Stanta, Giorgio; Vecchio, Giancarlo

doi:10.18632/oncotarget.24445

Cited by 11 publications

(9 citation statements)

References 32 publications

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“…In this cohort of 305 patients, 151 resulted to be negative for axillary locoregional lymph node involvement (LN-) at the time of diagnosis and 154 showed positive axillary locoregional lymph nodes (LN+) as already reported [8, 10]. Patients' mean age at diagnosis was 47 years (range 26-55).…”

Section: Resultsmentioning

confidence: 54%

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PI3K/AKT Signaling in Breast Cancer Molecular Subtyping and Lymph Node Involvement

et al. 2019

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Lymph node metastatic involvement persists to be among the most important predictors of recurrence and survival in breast carcinoma (BC). This study is aimed at investigating possible gene expression differences in primary BC between patients with or without lymph node involvement at the time of diagnosis. In a retrospective study, we investigated the potential prognostic role of 9 candidate biomarkers at the mRNA level in a cohort of 305 breast cancer patients, 151 lymph node-negative (LN-) and 154 lymph node-positive (LN+) individuals. The analyzed genes belonged to the RAS pathway (RAF1, ERBB2, PIK3CB, AKT1, AKT2, and AKT3), RB pathway (RB1 and CDK2), and cellular differentiation (KRT8). Their expression profiles were investigated by RT-qPCR and were correlated to immunohistochemically based molecular subtypes and BC clinical and pathological features. The differential expression of several genes in the primary tumor tissue was related to the LN involvement. Some of those genes, including PIK3CB, RB1, and AKT3, were more expressed in LN- BC patients, while some others, notably ERBB2 and AKT1, in LN+ ones. Among the candidate biomarkers, the expression levels of AKT isoforms influenced also patients' survival rates. In detail, higher expression levels of AKT1 and AKT2 negatively influenced overall patients' survival, and in particular, AKT2 expression levels defined a group of luminal B BC patients with shorter cancer-specific survival. On the contrary, longer cancer-specific survival was recorded in luminal A BC patients with higher expression levels of AKT3. That finding was also confirmed by Cox multivariate analysis. The same AKT3 resulted to be a possible candidate predictive biomarker for Tamoxifen response. In conclusion, our study highlighted the complex regulation of the PI3K/AKT pathway in BC and its differences in BC patients with and without lymph node involvement.

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Section: Resultsmentioning

confidence: 54%

“…The patients' cohort was followed for a maximum of 25 years through the local cancer registry from diagnosis of BC to death or until the censoring date. This study was approved by the Ethical Committee of the University of Trieste as already described [8, 10]. Follow-up data were reported in previous studies [8, 10].…”

Section: Methodsmentioning

confidence: 99%

PI3K/AKT Signaling in Breast Cancer Molecular Subtyping and Lymph Node Involvement

et al. 2019

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“…Based on data from previous works, it seems that no previous evidence about a relationship between α‐L‐FUCA‐1 and SS have yet been described. While genetic expression of α‐L‐FUCA‐1 has been recently correlated with tumors which suggests an important role of this glycosidase in chronic inflammatory response, fucosidase activity is closely related to lysosomal function, and its importance in the onset and progression of inflammation and autoimmune diseases has earlier been reviewed …”

Section: Discussionmentioning

confidence: 99%

“…Based on data from previous works, it seems that no previous evidence about a relationship between α-L-FUCA-1 and SS have yet been described. While genetic expression of α-L-FUCA-1 has been recently correlated with tumors 27,28 which suggests an important role of this glycosidase in chronic inflammatory response, fucosidase activity is closely related to lysosomal function, and its importance in the onset and progression of inflammation and autoimmune diseases has earlier been reviewed. 29 Interestingly, in SS the chronic inflammatory state is exacerbated by lysosome function, which in animal models has been shown to Statistics were calculated in a triplicate experiment with a minimal size of 10-20 samples, according to methods described in the text.…”

Section: Discussionmentioning

confidence: 99%

Plasma α‐L‐fucosidase‐1 in patients with Sjögren's syndrome and other rheumatic disorders

et al. 2019

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Background Human α‐fucosidase (EC 3.2.1.51) is a hydrolase the importance of which has been increasing in the latest years. However, data about its plasma level in children with autoimmune disorders, particularly Sjögren's syndrome (SS), are lacking. In this study, the plasma activity of L‐α‐fucosidase‐1 (α‐L‐FUCA‐1) was assayed in hospitalized children and adults and its association with SS and other rheumatic disorders further evaluated. Methods In total 73 Hungarian hospitalized patients, 32 children (2.5‐10 years) and 41 adults (32‐68 years), were enrolled in the study and underwent plasma assay of α‐L‐FUCA1 activity. Linear regression, Durbin‐Watson (DW), and Pearson tests were evaluated to investigate the relationship between α‐L‐FUCA‐1 plasma levels and autoimmune manifestations. Results α‐L‐FUCA‐1 correlated with SS both in children (2‐sided t test, P = 0.0023) and in adults (2‐sided t test, P = 0.00035). Linear regressions showed that in other rheumatic disorders, α‐L‐FUCA1 did not show any differential distribution related to the particular pathology (r = 0.2042, P = 0.1531, DW test = 2.2139 positive), while this trend was radically opposite for patients with SS (r = 0.1462, P = 0.0032, DW test = 1.3664, negative). Conclusions Alterations in plasma level of α‐L‐FUCA‐1 were significantly associated with SS. This preliminary result should encourage further research on α‐L‐FUCA‐1 as a possible differential serological marker of SS.

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“…13 Low FUCA1 expression is associated with a poor prognosis in TNBC compared to non-TNBC presentations, 14 while positive FUCA1 expression is associated with better survival for breast cancer patients with the luminal B lymph node-positive subtype compared to the luminal B lymph node-negative subtype. 15 FUCA1 is downstream of p53, with its expression induced by chemotherapeutic drugs. 16 Overexpression of FUCA1 suppresses the growth of cancer cell lines, 17 suggesting its importance in senescence induction and maintenance.…”

Section: Introductionmentioning

confidence: 99%

N-Linked glycosylation profiles of therapeutic induced senescent (TIS) triple negative breast cancer cells (TNBC) and their extracellular vesicle (EV) progeny

et al. 2021

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Reduced expression of α-L-Fucosidase-1 (FUCA-1) predicts recurrence and shorter cancer specific survival in luminal B LN+ breast cancer patients

Cited by 11 publications

References 32 publications

PI3K/AKT Signaling in Breast Cancer Molecular Subtyping and Lymph Node Involvement

PI3K/AKT Signaling in Breast Cancer Molecular Subtyping and Lymph Node Involvement

Plasma α‐L‐fucosidase‐1 in patients with Sjögren's syndrome and other rheumatic disorders

N-Linked glycosylation profiles of therapeutic induced senescent (TIS) triple negative breast cancer cells (TNBC) and their extracellular vesicle (EV) progeny

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