Identification of novel methylated DNA marker ZNF569 for head and neck squamous cell carcinoma

Abstract

Aberrant DNA methylation pattern plays an indispensable role in the initiation and development of head and neck squamous cell carcinoma (HNSCC). It is well recognized that lymph node metastasis is closely with unfavorable prognosis of HNSCC. Therefore, exploring the methylation events accounting for the lymph node metastasis of HNSCC is very important for improving the clinical outcome of HNSCC. Methylation data, RNA-seq data and clinical data were downloaded from The Cancer Genome Atlas (TCGA) and processed using the R package TCGA-Assembler. MethylMix was use for data analysis by integrating both methylation and gene expression data on HNSCC patients with lymph node metastasis and without lymph node metastasis. Pathway analysis was performed on significantly altered genes using ConsensusPathDB. The role of our interested gene zinc figure protein 569 (ZNF569) in HNSCC was further evaluated. Our results identified many novel hypermethylated/hypomethylated genes that might be closely associated with the lymph node metastasis of HNSCC. Pathway analysis revealed that increase in methylation of genes involved in generic transcription pathway including zinc figure proteins. ZNF569 was hypermethylated in HNSCC tissues especially those with lymph node metastasis. In addition, the expression levels of ZNF569 mRNA and protein were significantly lower in HNSCC tissues and cell lines compared to their respective controls. Moreover, overexpression of ZNF569 inhibited the proliferation, migration and invasion of HNSCC cells. HNSCC patients with lower ZNF569 expression suffered a significantly shorter overall survival than those with higher ZNF569 expression. In conclusion, we have identified many novel differentially methylated genes that might be important for the lymph node metastasis of HNSCC. In addition, ZNF569 might play a tumor suppressive role in carcinogenesis of HNSCC.

A DNA methylation-based test for esophageal cancer detection

“…Interestingly, we showed that ZNF569me levels could discriminate between ECa and normal esophagus with high specificity, regardless of the histotype, extending those previous reports. Furthermore, ZNF569 me was shown to play a tumor-suppressive role in head and neck squamous cell carcinoma [ 35 ] and a DNA-methylation based panel, which included ZNF569me , discriminated gastric adenocarcinoma from normal mucosa [ 36 ].…”

Identification and validation of an alternative splicing-based prognostic signature for head and neck squamous cell carcinoma

“…Head and neck cancer (HNC) is the sixth most common cancer around the world, and squamous cell carcinoma (HNSCC) accounts for more than 90% of all HNC cases [1,2]. It represents a leading reason for cancer-attributable morbidity and mortality, with a global incidence of 550 000 cases and 380 000 deaths annually [3].…”

A DNA Methylation-based Test for Esophageal Cancer Detection

“…Interestingly, we showed that ZNF569me levels could discriminate between ECa and normal esophagus with high speci city, regardless of the histotype, extending those previous reports. Furthermore, ZNF569me was shown to play a tumor-suppressive role in head and neck squamous cell carcinoma (36) and a DNA-methylation based panel, which included ZNF569me, discriminated gastric adenocarcinoma from normal mucosa (37).…”