Overexpression of N-cadherin and β-catenin correlates with poor prognosis in patients with nasopharyngeal carcinoma

Sun, Hong; Li, Mingyu; Wu, Xuewen; Yang, Chunguang; Zhang, Yanni; Xu, Zhenhang; Gao, Kelei; Wang, Fengjun

doi:10.3892/ol.2017.5645

Cited by 23 publications

(29 citation statements)

References 31 publications

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“…Consistent with our finding, results of previous studies investigated N-cadherin expression in other cancers including gastric, prostate , oral carcinomas, [23,24,27] nasopharyngeal carcinoma, [28,29] breast cancer, lung cancer reported similar findings of increased N-cadherin expression in tumor in comparison to adjacent non tumor tissue.…”

Section: Discussionsupporting

confidence: 82%

“…Many studies reported similar findings where N-cadherin expression showed significant correlations with the grade of differentiation, the clinical stage of disease, prognosis, survival rates and tendency to relapse. [4,20,29,37] High expression of N-cadherin was observed in 66.7% of the studied HNSCC cases that had positive nodal metastatic deposits but the p-value was not significant (p = .007) that may be due to the limited number of cases in our study. On the other hand, many studied revealed a significant association of N-cadherin to nodal metastasis.…”

Section: Discussioncontrasting

confidence: 37%

“…On the other hand, many studied revealed a significant association of N-cadherin to nodal metastasis. [4,20,29] Tumor progression is accomplished by several mechanisms; extracellular matrix (ECM) modification is one of the theses mechanisms. HA is a major component of ECM s and a member of the glycosaminoglycan family of polysaccharides.…”

Section: Discussionmentioning

confidence: 99%

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N-cadherin and hyaluronan expression in head and neck squamous cell carcinoma, relation to patient outcomes

Hendawy

Ibrahiem

et al. 2017

JST

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Background: Epithelial-mesenchymal transition (EMT) is regarded as an essential step for tumor invasion and metastasis. In squamous cell carcinoma of head and neck (HNSCC), N-Cadherin expression and its involvement in tumor progression remains a controversial topic. Aim of the study: The present study aimed to assess the expression of N-cadherin and HA in HNSCC and further study their relation to patients survival and outcomes. Material and methods: Fifty-eight retrospective selected cases of head and neck squamous carcinomas (HNSCCs) with available paraffin blocks. Complete clinico-pathological and follow-up data were recorded. Immune staining for N-cadherin and hyaluronan were done, also, we study the correlation of the results with patients survival data. Results: Squamous cell carcinoma islands demonstrated high N-cadherin expression in 55.2% and low expression in 44.8%. N-cadherin high expression was significantly (p < .05) associated with large tumor sizes, advanced TNM clinical stage, increased incidence of recurrence and patient's death. A significant correlation was recorded between the presence of neural invasion and N-cadherin expression (p = .004). Strong intensity of stromal HA was significantly (p < .05) associated with an oral site, nodal metastasis, and higher TNM stage. Patients with high N-cadherin expression, diffuse hyaluronan, and strong stromal hyaluronan reaction had significantly lower DFS rates (p < .05). High N-cadherin expression, diffuse hyaluronan immunoreactivity, and strong stromal hyaluronan reaction intensity had significantly lower OS rates (p < .05). Conclusion: N-cadherin and hyaluronan could be important and promising biomarkers during surveillance of patients with HNSCC.

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Section: Discussionsupporting

confidence: 82%

Section: Discussioncontrasting

confidence: 37%

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N-cadherin and hyaluronan expression in head and neck squamous cell carcinoma, relation to patient outcomes

Hendawy

Ibrahiem

et al. 2017

JST

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“…Although the Wnt/β-catenin signaling has been linked to the radiation resistance in NPC [17,18], there is no knowledge regarding the effect of β-catenin overexpression on radiation resistance in NPC to date. In addition, the associations of β-catenin expression with the biological behaviors of NPC cells and the prognosis of NPC patients remain controversial until now [12][13][14][15][16].…”

Section: Discussionmentioning

confidence: 99%

“…As a critical component in the Wnt/β-catenin signaling pathway [11], β-catenin has been linked strongly to the prognosis of NPC [12][13][14]; however, some studies argued that β-catenin had no associations with survival of NPC patients [15] and did not affect the invasion and metastasis of NPC cells [16]. In addition, the Wnt/β-catenin signaling has been found to be involved in NPC radioresistance [17,18].…”

Section: Introductionmentioning

confidence: 99%

Overexpression of β-Catenin Decreases the Radiosensitivity of Human Nasopharyngeal Carcinoma CNE-2 Cells

Kang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Nasopharyngeal carcinoma (NPC) is rare worldwide but remains highly prevalent in endemic regions, notably in southern China. Radiotherapy remains the treatment of choice for NPC, but radioresistance has been identified as a major cause of therapeutic failure. The Wnt/β-catenin signaling has been found to be involved in NPC radioresistance; however, the effect of β-catenin overexpression on radioresistance remains unknown in NPC until now. This study aimed to examine the impact of β-catenin overexpression on the radiosensitivity of human NPC CNE-2 cells. Methods: Immunohistochemistry was performed to detect the β-catenin expression in normal nasopharyngeal specimens and NPC specimens. The human NPC CNE-2 cell line overexpressing β-catenin was modeled by transfection with the pcDNA3.1/Hygro(+)/β-catenin recombinant vector (transfection group), while cells transfected with the pcDNA3.1/Hygro(+) vector served as negative controls and non-transfected cells served as blank controls. The expression of key molecules of the Wnt/β-catenin signaling pathway was determined using Western blotting and qPCR assays, and the changes of radiation sensitivity were measured with a colony-formation assay. Cell viability was measured by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 -diphenyltetrazolium bromide) assay. In addition, the cell cycle and apoptosis was detected using flow cytometry and the TCF/LEF transcriptional activity was measured with a Dual Luciferase Reporter Assay System. Results: Immunohistochemical staining showed high β-catenin expression in radioresistant NPC specimens, and low expression in radiosensitive NPC specimens and normal nasopharyngeal specimens. Western blotting and qPCR assays detected higher β-catenin expression in the transfection group than in the negative and blank controls (P < 0.01). Down-regulation of GSK-3β expression (P < 0.05) and up-regulation of Cyclin D1 expression (P < 0.01) was detected in β-catenin overexpressing NPC cells exposed to X-ray radiation relative to negative and blank controls. Colony-formation assay revealed higher D₀, D_q and SF in the transfection group than in the negative and blank control groups post-radiation, and the SER in the transfection group was 0.75-fold and 0.68-fold greater than that in the blank and negative control groups, respectively. MTT assay revealed that the viability of CNE-2 cells was significantly higher in the transfection group (96% ± 8.72%) than in the negative control group (74.67 ± 7.05%) and the blank control group (75.33% ± 7.02%) 24 h post-exposure to 6 Gy X-ray radiation (P < 0.05). X-ray radiation led to a lower proportion of CNE-2 cells at the G2/M phase and a lower apoptotic rate in the transfection group than in the negative and blank control groups (P < 0.05). In addition, the TCF/LEF transcriptional activity was higher in the transfection group than in the negative and blank control groups (P < 0.01), and 6 Gy X-ray radiation elevated the TCF/LEF transcriptional activity relative to 0 Gy radiation ...

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Telomerase reverse transcriptase mutations are independent predictor of disease‐free survival in Middle Eastern papillary thyroid cancer

Siraj

Divya

et al. 2017

Intl Journal of Cancer

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Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Tumor recurrence occurs in ∼20% of PTCs and some reach advanced stages. Promoter mutation in the telomerase reverse transcriptase (TERT) gene is identified to be a prognostic marker in PTC. However, the contribution of TERT promoter mutation to cancer progression in PTC patients is still not fully understood. In this study, we investigated the incidence of TERT promoter mutations and TERT protein expression and their association with clinicopathological outcomes in a large cohort of PTC samples using direct sequencing technology and immunohistochemistry. Furthermore, two PTC cell lines were utilized to investigate role of TERT mutations in mediating metastasis. Two promoter hotspot mutations C228T and C250T were identified in 18.0% (167/927) of our cohort and were significantly associated with poor 5 years disease-free survival and distant metastasis of PTC. TERT protein overexpression was noted in 20.1% of our PTC cohort and was significantly associated with poor prognostic markers such as older age, extrathyroidal extension and Stage IV tumors. A significant association was also found between TERT overexpression and epithelial-mesenchymal transition (EMT) markers. Functional analysis showed that TERT inhibition reduced cell growth, invasion, migration and angiogenesis in PTC via suppression of EMT in PTC cells. Our results suggest that TERT promoter mutation is an independent predictor of disease-free survival and might drive the metastasis, and downregulation of TERT could potentiate antitumor and antimetastatic activities in PTC.

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Overexpression of N-cadherin and β-catenin correlates with poor prognosis in patients with nasopharyngeal carcinoma

Cited by 23 publications

References 31 publications

N-cadherin and hyaluronan expression in head and neck squamous cell carcinoma, relation to patient outcomes

N-cadherin and hyaluronan expression in head and neck squamous cell carcinoma, relation to patient outcomes

Overexpression of β-Catenin Decreases the Radiosensitivity of Human Nasopharyngeal Carcinoma CNE-2 Cells

Telomerase reverse transcriptase mutations are independent predictor of disease‐free survival in Middle Eastern papillary thyroid cancer

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