Recurrent transcriptional loss of thePCDH17tumor suppressor in laryngeal squamous cell carcinoma is partially mediated by aberrant promoter DNA methylation

2018 ◽  
Vol 57 (7) ◽  
pp. 878-885 ◽  
Author(s):  
Ewa Byzia ◽  
Natalia Soloch ◽  
Magdalena Bodnar ◽  
Marcin Szaumkessel ◽  
Katarzyna Kiwerska ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Promoter Dna Methylation ◽  
Promoter Dna

Utility of MS-MLPA in DNA methylation profiling in primary laryngeal squamous cell carcinoma

Oral Oncology ◽  
2014 ◽  
Vol 50 (4) ◽  
pp. 291-297 ◽  
Author(s):  
Fernando López ◽  
Teresa Sampedro ◽  
José L. Llorente ◽  
Francisco Domínguez ◽  
Mario Hermsen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Dna Methylation Profiling ◽  
Methylation Profiling

scholarly journals Development and validation of epigenetic signature predict survival for patients with laryngeal squamous cell carcinoma

2020 ◽  
Author(s):  
Jie Cui ◽  
Liping Wang ◽  
Waisheng Zhong ◽  
Zhen Chen ◽  
Jie Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Squamous Cell Carcinoma ◽  
Small Molecules ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Cox Regression ◽  
Tnm Stage ◽  
Survival Prediction

Abstract Background: Epigenetic alterations, such as DNA methylation patterns, yield an important role in the initiation, progression and prognosis of laryngeal squamous cell carcinoma (LSCC). We performed a genome-wide integrated analysis of methylation and the transcriptome to establish epigenetic signature to improve the accuracy of survival prediction and optimize therapeutic strategies for LSCC.Methods: LSCC DNA methylation datasets and RNA sequencing (RNA-seq) datasets were acquired from the Cancer Genome Atlas (TCGA). MethylMix was applied to detect DNA methylation-driven genes (MDGs). By univariate and multivariate Cox regression analyses, five genes of DNA MDGs was developed an epigenetic signature. The predictive accuracy and clinical value of the epigenetic signature were evaluated by receiver operating characteristic (ROC) and decision curve analysis (DCA), and compared with TNM stage system. Additionally, prognostic value of the epigenetic signature was validated by external Gene Expression Omnibus (GEO) database. According to 5 MDGs of epigenetic signature, the candidate small molecules for LSCC were screen out by the CMap database.Results: A total of 88 DNA MDGs were identified, five of which (MAGEB2, SUSD1, ZNF382, ZNF418 and ZNF732) were chosen to construct an epigenetic signature. The epigenetic signature can effectively divide patients into high-risk and low-risk group, with the area under curve (AUC) of 0.8 (5-year OS) and AUC of 0.745 (3-year OS). Stratification analysis affirmed that the epigenetic signature was still a significant statistical prognostic model in subsets of patients with different clinical variables. Multivariate Cox regression analysis indicated the efficacy of epigenetic signature appears independent of other clinicopathological characteristics. In terms of predictive capacity and clinical usefulness, the epigenetic signature was superior to traditional TNM stage. Additionally, the epigenetic signature was confirmed in external LSCC cohorts from GEO. Finally, CMap matched the 10 most significant small molecules as promising therapeutic drugs to reverse the LSCC gene expression.Conclusion: An epigenetic signature, with five DNA MDGs, was identified and validated in LSCC patients by integrating multidimensional genomic data. Compared TNM stage alone, it generates more accurate estimations of the survival probability and maybe offer novel research directions and prospects for individualized treatment of patients with LSCC.

scholarly journals Recurrent epigenetic silencing of the PTPRD tumor suppressor in laryngeal squamous cell carcinoma

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769142 ◽  
Author(s):  
Marcin Szaumkessel ◽  
Sonia Wojciechowska ◽  
Joanna Janiszewska ◽  
Natalia Zemke ◽  
Ewa Byzia ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Squamous Cell Carcinoma ◽  
Tumor Suppressor ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Carcinoma Cell ◽  
Loss Of Function ◽  
Squamous Cell Carcinoma Cell ◽  
Carcinoma Cell Lines

Cellular processes like differentiation, mitotic cycle, and cell growth are regulated by tyrosine kinases with known oncogenic potential and tyrosine phosphatases that downmodulate the first. Therefore, tyrosine phosphatases are recurrent targets of gene alterations in human carcinomas. We and others suggested recently a tumor suppressor function of the PTPRD tyrosine phosphatase and reported homozygous deletions of the PTPRD locus in laryngeal squamous cell carcinoma. In this study, we investigated other gene-inactivating mechanisms potentially targeting PTPRD, including loss-of-function mutations and also epigenetic alterations like promoter DNA hypermethylation. We sequenced the PTPRD gene in eight laryngeal squamous cell carcinoma cell lines but did not identify any inactivating mutations. In contrast, by bisulfite pyrosequencing of the gene promoter region, we identified significantly higher levels of methylation (p = 0.001 and p = 0.0002, respectively) in 9/14 (64%) laryngeal squamous cell carcinoma cell lines and 37/79 (47%) of primary laryngeal squamous cell carcinoma tumors as compared to normal epithelium of the upper aerodigestive tract. There was also a strong correlation (p = 0.0001) between methylation and transcriptional silencing for the PTPRD gene observed in a cohort of 497 head and neck tumors from The Cancer Genome Atlas dataset suggesting that DNA methylation is the main mechanism of PTPRD silencing in these tumors. In summary, our data provide further evidence of the high incidence of PTPRD inactivation in laryngeal squamous cell carcinoma. We suggest that deletions and loss-of-function mutations are responsible for PTPRD loss only in a fraction of cases, whereas DNA methylation is the dominating mechanism of PTPRD inactivation.

Effect of miR-1266 on proliferation, invasion and migration of laryngeal squamous cell carcinoma by targeting CCL18

2020 ◽  
Vol 75 (2) ◽  
Author(s):  
Qijun Wang ◽  
Baifang Su ◽  
Qinggang Li ◽  
Qingjuan He ◽  
Dongmei Li ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Invasion And Migration ◽  
And Migration
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