Epithelial–Mesenchymal Expression Phenotype of Primary Melanoma and Matched Metastases and Relationship with Overall Survival

Yan, Shaofeng; Holderness, Britt M.; Li, Zhongze; Seidel, Gregory D.; Gui, Jiang; Fisher, Jan L.; Ernstoff, Marc S.

doi:10.21873/anticanres.11243

Cited by 34 publications

(20 citation statements)

References 31 publications

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“…As far as we know, this study is the first comprehensive and most full‐scale meta‐analysis to investigate the prognostic value of N‐cadherin upregulation in epithelial‐derived solid tumours. At the beginning, 38 studies were involved in this meta‐analysis, while 2 studies were about nonepithelial solid tumours, including melanoma and sarcoma . Thus, we excluded these 2 studies for making our conclusions more applicable to epithelia‐derived solid tumours.…”

Section: Discussionmentioning

confidence: 99%

“…At the beginning, 38 studies were involved in this meta-analysis, while 2 studies were about nonepithelial solid tumours, including melanoma and sarcoma. 77,78 Thus, we excluded these 2 studies for making our conclusions more applicable to epithelia-derived solid tumours. In summary, upregulation of N-cadherin was shown to be significantly associated with lymph node metastasis, higher histological grade, angiolymphatic invasion and advanced clinical stage.…”

Section: Discussionmentioning

confidence: 99%

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Upregulated N‐cadherin expression is associated with poor prognosis in epithelial‐derived solid tumours: A meta‐analysis

Luo

Zhang

et al. 2018

Eur J Clin Investigation

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BackgroundN‐cadherin is an important molecular in epithelial‐mesenchymal transition (EMT) and has been reported to be associated with aggressive behaviours of tumours. However, prognostic value of N‐cadherin in solid malignancies remains controversially.Materials and MethodsThe Pubmed/MELINE and EMBASE databases were used for a comprehensive literature searching. Pooled risk ratio (RR) and hazard ratio (HR) with their corresponding 95% confidence intervals (CIs) were employed to quantify the prognostic role.ResultsInvolving 36 studies with 5705 patients were performed to investigate relationships between N‐cadherin upregulation and clinicopathological features, survival. Results suggested upregulated N‐cadherin was associated with lymph node metastasis (RR = 1.16, 95% CI [1.00, 1.35]), higher histological grade (RR = 1.36, 95%CI [1.14, 1.62]), angiolymphatic invasion (RR = 1.19, 95% CI [1.06, 1.34]) and advanced clinical stage (RR = 1.32, 95% CI [1.06, 1.64]), while upregulated N‐cadherin was apt to be associated with distant metastasis (RR = 1.43, 95% CI [0.99, 2.05]). Moreover, N‐cadherin was correlated with poor prognosis of 3‐year survival (HR = 1.78, 95% CI [1.51, 2.10]), 5‐year survival (HR = 1.57, 95% CI [1.17, 2.10]) and overall survival (OS) (HR = 1.32, 95% CI [1.20, 1.44]). Subgroup analyses according to cancer types were also conducted for applying these conclusions to some tumours more properly. No publication bias was found except subgroup analysis of distant metastasis (P = .652 for Begg's test and 0.023 for Egger's test).ConclusionsTaken together, upregulation of N‐cadherin is associated with more aggressive behaviours of epithelial‐derived solid malignancies and can be regarded as a predictor of poor survival.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Upregulated N‐cadherin expression is associated with poor prognosis in epithelial‐derived solid tumours: A meta‐analysis

Luo

Zhang

et al. 2018

Eur J Clin Investigation

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“…E‐cadherin, an important member of the calcium‐dependent cell adhesion molecule family, is a well‐researched inhibitor of cell migration and invasion. Decreased E‐cadherin expression accompanied by increased N‐cadherin expression is the most important molecular event of the EMT . Snail is the direct repression of E‐cadherin and another important mediator of the EMT, as reviewed by Haraguchi .…”

Section: Discussionmentioning

confidence: 99%

FAM3B promotes progression of oesophageal carcinoma via regulating the AKT–MDM2–p53 signalling axis and the epithelial‐mesenchymal transition

Wang

Yang

et al. 2018

J Cellular Molecular Medi

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FAM3B has been suggested to play important roles in the progression of many cancers, such as gastric, oral, colon and prostate cancer. However, little is known about the role of FAM3B in human esophageal squamous cell carcinoma (ESCC). In the present study, we found that FAM3B expression was higher in ESCC tissues than in adjacent normal tissues. Using quantitative real‐time polymerase chain reaction, we found similar results in cell lines. FAM3B expression was significantly related to T/TNM stage. Importantly, Kaplan–Meier analysis revealed that a high expression level of FAM3B predicted a poor outcome for ESCC patients. Overexpression of FAM3B inhibits ESCC cell death, increases oesophageal tumour growth in xenografted nude mice, and promotes ESCC cell migration and invasion. Further studies confirmed that FAM3B regulates the AKT–MDM2–p53 pathway and two core epithelial‐to‐mesenchymal transition process markers, Snail and E‐cadherin. Our results provide new insights into the role of FAM3B in the progression of ESCC and suggest that FAM3B may be a promising molecular target and diagnostic marker for ESCC.

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“…EMT phenotype switching has been shown to be involved 328 in acquisition of metastatic properties in the vertical growth phase of SKCM (Bennett, 329 2008) and loss of E-cadherin, with gain of N-cadherin and osteonectin, was associated 330 with SKCM metastasis (Alonso et al, 2007). Importantly, the presence of aberrant E-331 cadherin expression in primary and metastatic SKCM is associated with a poor overall 332 patient survival (Yan et al, 2016). Therefore, our results suggest that SPINT1 loss may 333 facilitate metastatic invasion of human SKCM through EMT phenotype switching.…”

mentioning

confidence: 82%

SPINT1 regulates the aggressiveness of skin cutaneous melanoma and its crosstalk with tumor immune microenvironment

Gómez-Abenza

Ibáñez-Molero

García‐Moreno

et al. 2019

Preprint

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statement (15-30 words) 29 A zebrafish model shows that Spint1a deficiency facilitates oncogenic transformation, 30 regulates the tumor/immune microenvironment crosstalk, accelerates the onset of 31 SKCM, and promotes metastatic invasion in cell autonomous and non-autonomous 32 manners.Abstract 35 Skin cutaneous melanoma (SKCM) is the deadliest form of skin cancer and 36 while incidence rates are declining for most cancers, they have been steadily rising for 37 SKCM worldwide. Serine protease inhibitor, kunitz-type, 1 (SPINT1) is a type II 38 transmembrane serine protease inhibitor that has been shown to be involved in the 39 development of several types of cancer. We report here a high prevalence of SPINT1 40 genetic alterations in SKCM patients and their association with altered tumor immune 41 microenvironment and poor patient survival. We used the unique advantages of the 42 zebrafish to model the impact of SPINT1 deficiency in early transformation, 43 progression and metastatic invasion of SKCM. Our results reveal that Spint1a 44 deficiency facilitates oncogenic transformation, regulates the tumor/immune 45 microenvironment crosstalk, accelerates the onset of SKCM and promotes metastatic 46 invasion. Notably, Spint1a deficiency is required at both cell autonomous and non-47 autonomous levels to enhance invasiveness of SKCM. These results suggest the 48 relevance of clinical intervention on this signaling pathway for precision SKCM 49 medicine. 50 51 52 53 54 55 Skin cutaneous melanoma (SKCM) originates from melanocytes, neural-crest 56 derived pigment-producing cells located in the epidermis, where their major function is 57 to protect keratinocytes from UV-induced DNA damage (Wellbrock and Arozarena, 58 2016). The malignant transformation of melanocytes generates this fatal form of skin 59 cancer with a complex multigenic etiology that becomes extremely difficult to treat 60 once it has metastasized. SKCM is the deadliest form of skin cancer (75% of deaths 61 related to skin cancer) and it is common in the Western world. Indeed, its global 62 incidence is 15-25 per 100,000 individuals (Schadendorf and Hauschild, 2014). While 63 incidence rates are declining for most cancers, they have been steadily rising for SKCM 64 worldwide (van Rooijen et al., 2017). Early detection is fundamental, since localized, 65 early stage SKCM can be surgically excised with little chance of recurrence with a 66 98.2% of patient survival rate after 5 year survival as reported by The Surveillance, 67 Epidemiology, and End Results (SEER) (NIH, 2019). Metastatic SKCM, however, is 68 still an often fatal disease with a 5-year survival rate of 15-20% (van Rooijen et al., 69 2017). 70 SKCM is one of the most recurrent types of cancer and its genetic heterogeneity 71 has led in recent years to join forces to determine SKCM causes and develop effective 72 therapies. Transformation of melanocytes into primary and then metastatic SKCM 73 requires a complex interplay of exogenous and endogenous events (Schadendorf et al., 74 2015). More ...

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Epithelial–Mesenchymal Expression Phenotype of Primary Melanoma and Matched Metastases and Relationship with Overall Survival

Cited by 34 publications

References 31 publications

Upregulated N‐cadherin expression is associated with poor prognosis in epithelial‐derived solid tumours: A meta‐analysis

Upregulated N‐cadherin expression is associated with poor prognosis in epithelial‐derived solid tumours: A meta‐analysis

FAM3B promotes progression of oesophageal carcinoma via regulating the AKT–MDM2–p53 signalling axis and the epithelial‐mesenchymal transition

SPINT1 regulates the aggressiveness of skin cutaneous melanoma and its crosstalk with tumor immune microenvironment

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