Wnt3a protein overexpression predicts worse overall survival in laryngeal squamous cell carcinoma

Zhang, Diekuo; Li, Guo; Chen, Xiyu; Jing, Qiancheng; Liu, Chao; Lu, Shanhong; Huang, Donghai; Wang, Yunyun; Tan, Pingqing; Chen, Jie; Zhang, Xin; Qiu, Yuanzheng; Liu, Yong

doi:10.7150/jca.35009

Cited by 9 publications

(7 citation statements)

References 38 publications

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“…Wnt/beta-catenin signaling was regulated by long non-coding RNA, which affects the proliferation of LSCC [ 22 , 23 ]. Overexpression of Wnt3a, one canonical Wnt/β-catenin signaling pathway, was association with the poor overall survival of LSCC patients [ 6 ]. In this analysis, we observed the significant enrichment of mTOR signaling pathway and Wnt signaling pathway of genes in two LSCC stage related modules: ‘darkorange’ and ‘lightyellow’ (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The long non-coding RNA CDKN2B-AS1 facilitates LSCC by regulating miR-497/CDK6 pathway and is associated with advanced clinical stage [ 5 ]. Patients with lymph node metastasis/advanced clinical stages and high Wnt3a expression had worse overall survival rates than patients with other features [ 6 ]. High FTH1P3 expression, positively correlated with advanced clinical stage, predicts a poor prognosis, and promotes aggressive phenotypes of LSCC [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

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Comprehensive analysis reveals COPB2 and RYK associated with tumor stages of larynx squamous cell carcinoma

et al. 2022

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Background Laryngeal squamous cell carcinoma (LSCC) is one of the highly aggressive malignancy types of head and neck squamous cell carcinomas; genes involved in the development of LSCC still need exploration. Methods We downloaded expression profiles of 96 (85 in advanced stage and 11 in early stage) LSCC patients from TCGA-HNSC. Function enrichment and protein-protein interactions of genes in significant modules were conducted. Univariate and multivariate Cox regression analyses were performed to explore potential prognostic biomarkers for LSCC. The expression levels of genes at different stages were compared and visualized via boxplots. Immune infiltration was examined by the CIBERSORTx web-based tool and depicted with ggplot2. Gene set enrichment analysis (GSEA) was utilized to analyze functional enrichment terms and pathways. Immunohistochemical staining (IHC) was used to verify the expression of genes in the LSCC samples. Results We identified 25 modules, including 3 modules significantly related to tumor stages of LSCC via weighted gene co-expression network analysis (WGCNA). UIMC1, NPM1, and DCTN4 in the module ‘cyan’, TARS in the module ‘darkorange’, and COPB2 and RYK in the module ‘lightyellow’ showed statistically significant relation to overall survival. The expression of COPB2, DCTN4, RYK, TARS, and UIMC1 indicated association with the change of fraction of immune cells in LSCC patients; two genes, COPB2 and RYK, indicated different expression in various tumor stages of LSCC. Finally, COPB2 and RYK showed high-expression in tumor tissues of advanced LSCC patients. Conclusions Our study provided a potential perceptive in analyzing progression of LSCC cells and exploring prognostic genes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis reveals COPB2 and RYK associated with tumor stages of larynx squamous cell carcinoma

et al. 2022

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“…WNT3A regulates the cell cycle and metastasis and acts as a prognostic marker of hepatocellular carcinoma [ 46 , 47 , 48 ]. In head and neck cancer, the level of WNT3A was increased in patients’ serum, which enhanced radioresistance by WNT/β-catenin pathway activation in NPC cells [ 49 ], and it may represent an independent prognostic factor in laryngeal squamous cell carcinoma [ 50 ]. Thus, aberrant expression of canonical WNT ligands tends to promote cancer aggressiveness, including enhanced cancer cell progression, metastasis, and poor clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

WNT8B as an Independent Prognostic Marker for Nasopharyngeal Carcinoma

et al. 2021

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Background: Members of the Wnt signaling pathway have been shown to play a role in nasopharyngeal carcinoma (NPC) progression. Aim: The purpose of this study was to investigate WNT8B protein expression in NPC patients using tissue microarray (TMA) analysis and to evaluate its correlation with patient survival and clinical parameters. Methods: A total of 82 NPC cases, together with six normal nasopharyngeal tissue samples, were targeted to construct the TMA blocks. The WNT8B protein expression was evaluated by immunohistochemistry and its correlation to the clinicopathological features was investigated. Results: Sixty-two of 82 (75.6%) cases exhibited high WNT8B protein expression while 20/82 (24.4%) cases appeared to have low WNT8B expression. The univariate analysis revealed that systemic metastasis was associated with patient 5-year survival. The multivariate Cox proportional hazard regression analysis showed that WNT8B expression and systemic metastasis were significantly associated with the survival of NPC patients. Furthermore, there was no correlation found between the WNT8B protein expression and other clinicopathological parameters. Conclusion: Our results suggest that the expression of WNT8B is associated with NPC patients’ survival and could serve as an independent prognostic factor for NPC patients.

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“…WNT ligands overexpression translocation of β-catenin lymph node invasion [61][62][63][64] APC mutational loss stabilization of β-catenin enhanced cell growth [10][11][12][13][14][15][16] FAT1 mutational loss reduced sequestration of β-catenin enhanced cell growth, loss of cell adhesion [60] CDH1 (epi)mutational loss release of β-catenin from cell-cell junctions enhanced cell growth, loss of cell adhesion [51,55,57,58] EGFR overexpression stabilization and nuclear translocation of β-catenin enhanced cell proliferation [13,18] c-MET overexpression Wnt activation via FZD8 increased stemness [99] SFRP1-5 epigenetic silencing reduced Wnt ligand sequestration worse prognosis [73] invasiveness, lymph node metastasis, recurrence, dedifferentiation [26,28,38,42,[44][45][46][47][48]…”

Section: Drivers Of Wnt Activationmentioning

confidence: 99%

“…Oral cavity tumors expressing Wnt ligands exhibited an increased level of cytoplasmic and nuclear β-catenin, and WNT-3 expression, together with nuclear β-catenin localization, were seen predominantly at the invasive tumor front [63]. High expression of WNT-3A in laryngeal tumors was associated with lymph node metastasis and shorter survival [64]. Also, dysplastic oral lesions showed much higher WNT-3A expression than normal mucosa [26,35].…”

Section: Introductionmentioning

confidence: 98%

The Significance of the Dysregulation of Canonical Wnt Signaling in Head and Neck Squamous Cell Carcinomas

Paluszczak

2020

Cells

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The knowledge about the molecular alterations which are found in head and neck squamous cell carcinomas (HNSCC) has much increased in recent years. However, we are still awaiting the translation of this knowledge to new diagnostic and therapeutic options. Among the many molecular changes that are detected in head and neck cancer, the abnormalities in several signaling pathways, which regulate cell proliferation, cell death and stemness, seem to be especially promising with regard to the development of targeted therapies. Canonical Wnt signaling is a pathway engaged in the formation of head and neck tissues, however it is not active in adult somatic mucosal cells. The aim of this review paper is to bring together significant data related to the current knowledge on the mechanisms and functional significance of the dysregulation of the Wnt/β-catenin pathway in head and neck tumors. Research evidence related to the role of Wnt signaling activation in the stimulation of cell proliferation, migration and inhibition of apoptosis in HNSCC is presented. Moreover, its role in promoting stemness traits in head and neck cancer stem-like cells is described. Evidence corroborating the hypothesis that the Wnt signaling pathway is a very promising target of novel therapeutic interventions in HNSCC is also discussed.Cells 2020, 9, 723 2 of 20 blocking the interaction between PD-1 receptor and PD-L1, may be beneficial in patients with advanced, metastatic or recurrent HNSCC [7]. However, other therapeutic options are also necessary for the better clinical management of HNSCC patients. To that end, molecular alterations observed in HNSCC need to be studied in detail, in order to point to promising drug targets. Mechanisms of Wnt/β-Catenin Pathway Activation in HNSCCRecent genomic analyses have shown the prevalence of genetic driver alterations in HNSCC, which most frequently affect genes associated with receptor tyrosine kinase (e.g., EGFR, MET, KIT), PI3K, p53, Notch or Hippo signaling pathways. On the other hand, genetic alterations in genes related to canonical Wnt signaling were rarely detected in HNSCC [8,9]. In contrast to colorectal cancers, which show molecular alterations driving Wnt signaling activation in around 90% of cases [9], HNSCC were shown to lack CTNNB1 mutations and APC mutations were present infrequently [10][11][12][13][14][15][16]. The mutations of FAT1 tumor suppressor, which encodes a protocadherin protein that binds and inactivates β-catenin, were detected in some cases of HNSCC [17]. However, the activation of the Wnt/β-catenin pathway in HNSCC seems to be more prevalent than it is suggested by genetic findings, due to cross-talk with other molecular alterations, which can lead to pathway cross-activation. Indeed, it has been shown that β-catenin can be activated via enhanced EGFR or PI3K signaling, which belong to the most frequently dysregulated signaling pathways in HNSCC. In this regard, elevated EGFR expression was associated with delocalized β-catenin expression [13]. In another study, the nuclear ...

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Wnt3a protein overexpression predicts worse overall survival in laryngeal squamous cell carcinoma

Cited by 9 publications

References 38 publications

Comprehensive analysis reveals COPB2 and RYK associated with tumor stages of larynx squamous cell carcinoma

Comprehensive analysis reveals COPB2 and RYK associated with tumor stages of larynx squamous cell carcinoma

WNT8B as an Independent Prognostic Marker for Nasopharyngeal Carcinoma

The Significance of the Dysregulation of Canonical Wnt Signaling in Head and Neck Squamous Cell Carcinomas

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