Hypermethylated ZNF582 and PAX1 genes in oral scrapings collected from cancer-adjacent normal oral mucosal sites are associated with aggressive progression and poor prognosis of oral cancer

Cheng, Shih‐Jung; Chang, Chih-Hung; Ko, Hui‐Hsin; Liu, Yi-Ching; Peng, Hsin‐Hui; Wang, Huei-Jen; Lin, Hsiao-Shan; Chiang, Chun‐Pin

doi:10.1016/j.oraloncology.2017.11.013

Cited by 20 publications

(26 citation statements)

References 33 publications

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“…ZNF582 was first reported to be hypermethylated and may serve as a biomarker for cervical cancer [32,33]. Emerging data suggested that ZNF582 was also hypermethylated in esophageal squamous cell carcinoma [11,34] and oral cancer [12,35]. In the present study, we also found that ZNF582 was hypermethylated in NPC and ZNF582 expression was significantly decreased in NPC tissues as compared with that in normal nasopharyngeal tissues.…”

Section: Discussionsupporting

confidence: 75%

ZNF582 hypermethylation promotes metastasis of nasopharyngeal carcinoma by regulating the transcription of adhesion molecules Nectin‐3 and NRXN3

Zhao¹,

Hong²,

et al. 2020

Cancer Communications

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Background Epigenetic regulation plays an important role in the development and progression of nasopharyngeal carcinoma (NPC). However, the epigenetic mechanisms underlying NPC metastasis remains poorly understood. We aimed to find functional genes which regulate the metastasis of NPC and identify therapeutic targets for NPC treatment. Methods Bisulfite pyrosequencing was used to analyze zinc finger protein 582 (ZNF582) methylation in NPC tissues and cell lines. Quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) and Western blotting were used to determine the expression of ZNF582. In vitro and in vivo experiments were performed to evaluate the biological function of ZNF582 in NPC. ZNF582‐targeting genes were identified by chromatin immunoprecipitation sequencing (ChIP‐seq) and were confirmed by ChIP‐qPCR and luciferase assay. Results ZNF582 promoter was hypermethylated in NPC, and both the mRNA and protein levels of ZNF582 were down‐regulated in NPC tissues and cell lines. The restoration of ZNF582 inhibited NPC migration, invasion, and metastasis, while the knockdown of ZNF582 promoted NPC migration, invasion, and metastasis in vitro and in vivo. ZNF582 directly regulated the transcription and expression of adhesion molecules Nectin‐3 and NRXN3. Both Nectin‐3 and NRXN3 were identified as functional targets of ZNF582, and the restoration or abrogation of these genes reversed the tumor suppressor effect of ZNF582 in NPC metastasis. Conclusions ZNF582 acts as a tumor suppressor gene in NPC by regulating the transcription and expression of adhesion molecules Nectin‐3 and NRXN3, which may provide novel therapeutic targets for NPC treatment.

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Section: Discussionsupporting

confidence: 75%

ZNF582 hypermethylation promotes metastasis of nasopharyngeal carcinoma by regulating the transcription of adhesion molecules Nectin‐3 and NRXN3

Zhao¹,

Hong²,

et al. 2020

Cancer Communications

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“…Our results showed that ZNF582 was highly methylated in tumor specimens with lymph node metastasis compared to those without lymph node metastasis. Consistent with our findings, the methylation level of ZNF582 was remarkably higher in moderate/severe dysplasia/oral cancer than mild dysplasia/normal control 17.…”

Section: Discussionsupporting

confidence: 92%

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

2019

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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.

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“…In particular, several studies have shown the potential of DNA methylation as a prognostic marker. For instance, methylation of PAX1, ZNF582, and p16 derived from different specimen sources such as serum or oral scrapings was shown promising as a prognostic marker for colorectal cancer or OSCC 15,27 . Furthermore, a longitudinal study has demonstrated that hypermethylated PAX1 or ZNF582 genes in oral scrapings collected from cancer‐adjacent normal 15 oral mucosal sites are associated with aggressive progression and poor prognosis of oral cancer.…”

Section: Discussionmentioning

confidence: 99%

“…For instance, methylation of PAX1, ZNF582, and p16 derived from different specimen sources such as serum or oral scrapings was shown promising as a prognostic marker for colorectal cancer or OSCC 15,27 . Furthermore, a longitudinal study has demonstrated that hypermethylated PAX1 or ZNF582 genes in oral scrapings collected from cancer‐adjacent normal 15 oral mucosal sites are associated with aggressive progression and poor prognosis of oral cancer. In this present study, we demonstrated that statistical correlations between methylation level of PAX1 or ZNF582 in tissue specimens and indicators of OSCC severity, including tumor size, stage, and bone invasion.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, several studies in Taiwan suggested that methylation of PAX1 and ZNF582 is potential biomarkers for OSCC detection 13 . Hypermethylation of PAX1 and ZNF582 genes in oral scrapings collected from cancer‐adjacent normal oral mucosal sites was associated with aggressive progression and poor prognosis 15‐17 . Whether hypermethylated PAX1 and ZNF582 collected from tumor tissue was associated with progression were still uncertain.…”

Section: Introductionmentioning

confidence: 99%

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Hypermethylated PAX1 and ZNF582 genes in the tissue sample are associated with aggressive progression of oral squamous cell carcinoma

Sun

Juan²,

Su³

et al. 2020

J Oral Pathology Medicine

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Background DNA methylation of paired box gene 1 (PAX1) and zinc finger 582 (ZNF582) is promising cancer biomarkers for oral squamous cell carcinoma detection. This study aims to investigate the correlation between PAX1 or ZNF582 methylation and the progression of oral squamous cell carcinoma (OSCC). Materials and Methods A total of 135 OSCC cases from Peking University School and Hospital of Stomatology were enrolled in this study. Tissue specimens were collected from the lesion site and corresponding adjacent normal site. The methylation level of these two genes was evaluated in primary and recurrent OSCC group. Results Hypermethylation of PAX1 or ZNF582 was observed in lesion sites among primary and recurrent OSCC cases. In the lesion site of primary cases, promoter methylation was observed in T3/T4 (PAX1: P = .02; ZNF582: P = .01), stage III/IV (PAX1: P = .03; ZNF582: P = .01), and bone invasion cases (PAX1: P = .02; ZNF582: P = .047). In the subgroup analysis, the correlation between hypermethylation and OSCC severity remains significant with exposure to smoking/alcohol consumption. Conclusions Hypermethylated PAX1 and ZNF582 can sufficiently act as biomarkers to reflect the severity or progression of OSCC.

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Hypermethylated ZNF582 and PAX1 genes in oral scrapings collected from cancer-adjacent normal oral mucosal sites are associated with aggressive progression and poor prognosis of oral cancer

Cited by 20 publications

References 33 publications

ZNF582 hypermethylation promotes metastasis of nasopharyngeal carcinoma by regulating the transcription of adhesion molecules Nectin‐3 and NRXN3

ZNF582 hypermethylation promotes metastasis of nasopharyngeal carcinoma by regulating the transcription of adhesion molecules Nectin‐3 and NRXN3

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

Hypermethylated PAX1 and ZNF582 genes in the tissue sample are associated with aggressive progression of oral squamous cell carcinoma

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