Recent studies indicate various molecular abnormalities in oral squamous cell carcinomas (OSCC), including DNA methylation of tumor-associated genes. Although promoter hypermethylation of Wnt pathway antagonists RUNX3 (Runt-related transcription factor 3) and Wnt inhibitory factor 1 (WIF1) has been identified as a common event in a number of carcinomas, methylation status and the role of RUNX3 as a possible tumor suppressor in oral and head and neck cancer are yet controversial. The aim of our study is to determine the occurrence of RUNX3 and WIF1 genes hypermethylation and correlation with tumor and host-related factors and prognosis in tongue carcinomas.
In 76 patients with tongue carcinoma, RUNX3 and WIF1 genes promoter hypermethylation analysis was assessed by nested methylation-specific PCR method.
Hypermethylation of WIF1 and RUNX3 genes promoters was observed in 35% and 25% of carcinomas, respectively. RUNX3 gene promoter hypermethylation was significantly associated with lymph node involvement (P = 0.013) and tumor stage (P = 0.006), but not with the overall survival. Occurrence of RUNX3 and WIF1 genes comethylation was associated with nodal status (P = 0.058) and tumor stage (P = 0.055).
Our findings indicate that RUNX3 and WIF1 are frequently aberrantly methylated and that RUNX3 promoter methylation could be considered as a potential prognostic marker in tongue carcinoma.
"As shown in Table 6, the differentially expressed genes (DEGs) were enriched in 215 pathways, of which 68 were found to be significantly enriched by KEGG pathway enrichment analysis. These included ECM-receptor pathway interaction and focal adhesion pathways, which have both been previously reported in OSCC    . "
[Show abstract][Hide abstract] ABSTRACT: Head and neck cancer is the sixth most common cancer worldwide and one of the most aggressive
malignancies in human population. The most common histologic type among the
head and neck tumors are the squamous cell carcinomas (SCC). Despite the significant efforts
committed during the last decades in its early detection, prevention and treatment,
head and neck cancer prognosis remains very poor with the rising incidence in developed
countries and younger population. Carcinogenesis of Head and Neck Squamous Cell Carcinoma
(HNSCC) is a multistep process, which arises through an accumulation of genetic and
epigenetic alterations. Although the impact of genetic changes in oral carcinogenesis is wellknown,
over the last decade it has been demonstrated that epigenetic changes, especially
aberrant DNA methylation, play a significant role in HNSCC.
Methylation - From DNA, RNA and Histones to Diseases and Treatment, Edited by Anica Dricu, 11/2012: chapter DNA Methylation in the Pathogenesis of Head and Neck Cancer: pages 185-216; InTech., ISBN: 978-953-51-0881-8
[Show abstract][Hide abstract] ABSTRACT: Background
Aberrations in the function of the WNT signaling pathway have been recently implicated in the pathogenesis of head and neck cancer, and the hypermethylation of several WNT cascade inhibitors were shown to be useful in disease prognosis. However, the extent of deregulation of WNT pathway by DNA hypermethylation has not been studied in detail in laryngeal cancer so far. The aim of this study was to establish the frequency of methylation of WNT pathway negative regulators in laryngeal squamous cell carcinomas and evaluate its prognostic significance.Methods
Twenty-six laryngeal squamous cell carcinoma cell lines and samples obtained from twenty-eight primary laryngeal carcinoma patients were analyzed. The methylation status of DKK1, LKB1, PPP2R2B, RUNX3, SFRP1, SFRP2, and WIF-1 was assessed using the methylation-specific polymerase chain reaction.ResultsFrequent hypermethylation of DKK1, PPP2R2B, SFRP1, SFRP2, and WIF-1 was detected, and a high methylation index was usually observed. Half of the cell lines analyzed and seventy percent of primary laryngeal carcinoma cases were characterized by the methylation of at least four genes. The hypermethylation of PPP2R2B or WIF-1 was associated with longer survival in laryngeal carcinoma cell lines. Moreover, the concurrent methylation of PPP2R2B and SFRP1 differentiated primary from recurrent laryngeal carcinoma cell lines.Conclusions
Frequent hypermethylation of WNT pathway negative regulators is observed in laryngeal squamous cell carcinomas. The possible prognostic significance of the methylation of DKK1, PPP2R2B, and SFRP1 needs to be evaluated in further prospective studies.
Journal of Oral Pathology and Medicine 04/2014; 43(9). DOI:10.1111/jop.12178 · 1.93 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.