Aberrant methylation of DACT1 and DACT2 are associated with tumor progression and poor prognosis in esophageal squamous cell carcinoma

Guo, Yanli; Shan, Baoen; Guo, Wei; Zhang, Dong; Zhou, Zhen; Shen, Supeng; Guo, Xin; Liang, Jia; Kuang, Gang

doi:10.1186/s12929-016-0308-6

Cited by 22 publications

(23 citation statements)

References 35 publications

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“…The reactivated DACT1 gene inhibited the invasion and metastasis of NPC cells. Guo et al [14] have found that abnormal methylation of the DACT1 gene was associated with the progress and poor prognosis of esophageal squamous cell carcinoma. Deng et al [15] found that the number of methylation sites in the CpG island of the DACT1 gene was related to the prognosis of the disease.…”

Section: Discussionmentioning

confidence: 99%

Effects of DACT1 methylation status on invasion and metastasis of nasopharyngeal carcinoma

Yang

Lin

Zhang³

2019

Biol Res

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Background The purpose of the present study was to investigate the role of the methylation status of the DACT1 gene on the invasion and metastasis of nasopharyngeal carcinoma cells. Methods The levels of methylation and expression of the DACT1 gene in nasopharyngeal carcinoma tissues and CNE2 cells were determined by methylation-specific PCR and RT-PCR, respectively. CNE2 cells were treated with 5-aza-2-deoxycytidine, and the variation in the methylation status of the DACT1 gene was detected, as well as the influence of methylation on invasiveness of nasopharyngeal carcinoma cells. Results The DACT1 gene was hyper-methylated in 44 of 62 cases of nasopharyngeal carcinoma. The DACT1 gene was hyper-methylated in 32 of 38 cases of nasopharyngeal carcinoma with lymph node metastasis, and the DACT1 gene was hyper-methylated in 7 of 24 cases of nasopharyngeal carcinoma without lymph node metastasis. The DACT1 mRNA level was weakly expressed or not expressed in all nasopharyngeal carcinoma tissues with hyper-methylated DACT1 genes; however, the DACT1 mRNA level was highly expressed in nasopharyngeal carcinoma tissues with low expression of the methylated DACT1 gene. The DACT1 gene was hyper-methylated and not expressed in CNE2 cells that did not have 5-aza-2-deoxycytidine treatment. After 5-aza-2-deoxycytidine treatment, the DACT1 gene was demethylated and the expression of DACT1 was restored. Moreover, the invasion ability was inhibited in CNE2 cells treated with 5-aza-2-deoxycytidine. Conclusion The expression of DACT1 was related to the methylation status. High expression of DACT1 may inhibit the invasion and metastasis of nasopharyngeal carcinoma cells.

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Section: Discussionmentioning

confidence: 99%

Effects of DACT1 methylation status on invasion and metastasis of nasopharyngeal carcinoma

Yang

Lin

Zhang³

2019

Biol Res

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“…The genes corresponding to the five methylation sites (cg05008070, cg07227049, cg13759702, cg16376000, and cg23170347) were DACT1, VRK2, MELTF, FGF12, and PRICKLE2, which were all protein coding genes. DACT1, VRK2, MELTF, and FGF12 have been implicated in cancers other than CC (Dmitriev et al, 2015;Fernandez et al, 2010;Guo et al, 2017), and PRICKLE2 has been reported to correlate with CC (Senchenko et al, 2013). Future studies will be required to elucidate the functional impact of aberrant methylation of these five genes in CC development.…”

Section: Risk Stratificationmentioning

confidence: 99%

HPV‐related methylation‐based reclassification and risk stratification of cervical cancer

Yang

Wang

et al. 2020

Molecular Oncology

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Human papillomavirus (HPV) is a clear etiology of cervical cancer (CC). However, the associations between HPV infection and DNA methylation have not been thoroughly investigated. Additionally, it remains unknown whether HPV‐related methylation signatures can identify subtypes of CC and stratify the prognosis of CC patients. DNA methylation profiles were obtained from The Cancer Genome Atlas to identify HPV‐related methylation sites. Unsupervised clustering analysis of HPV‐related methylation sites was performed to determine the different CC subtypes. CC patients were categorized into cluster 1 (Methylation‐H), cluster 2 (Methylation‐M), and cluster 3 (Methylation‐L). Compared to Methylation‐M and Methylation‐L, Methylation‐H exhibited a significantly improved overall survival (OS). Gene set enrichment analysis (GSEA) was conducted to investigate the functions that correlated with different CC subtypes. GSEA indicated that the hallmarks of tumors, including KRAS signaling, TNFα signaling via NF‐κB, inflammatory response, epithelial–mesenchymal transition, and interferon‐gamma response, were enriched in Methylation‐M and Methylation‐L. Based on mutation and copy number variation analyses, we found that aberrant mutations, amplifications, and deletions among the MYC, Notch, PI3K‐AKT, and RTK‐RAS pathways were most frequently detected in Methylation‐H. Additionally, mutations, amplifications, and deletions within the Hippo, PI3K‐AKT, and TGF‐β pathways were presented in Methylation‐M. Genes within the cell cycle, Notch, and Hippo pathways possessed aberrant mutations, amplifications, and deletions in Methylation‐L. Moreover, the analysis of tumor microenvironments revealed that Methylation‐H was characterized by a relatively low degree of immune cell infiltration. Finally, a prognostic signature based on six HPV‐related methylation sites was developed and validated. Our study revealed that CC patients could be classified into three heterogeneous clusters based on HPV‐related methylation signatures. Additionally, we derived a prognostic signature using six HPV‐related methylation sites that stratified the OS of patients with CC into high‐ and low‐risk groups.

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“…DNA methylation is usually considered as a silencing epigenetic marker in diseases like cancer [12]. For example, the methylation of Dishevelled Binding Antagonist of Beta Catenin (DACT) 1and DACT 2 was associated with the development of esophageal squamous cell carcinoma (ESCC) and was regarded as prognostic biomarkers of ESCC [13]. Methylation of DNA repair gene O-6-methylguanine-DNA methyltransferase (MGMT) promoter region has been correlated with better prognosis of glioblastoma multiforme [14].…”

Section: Introductionmentioning

confidence: 99%

Promoter Methylation of Ezrin and its Impact on the Incidence and Prognosis of Cervical Cancer

Qin¹,

Cao²,

Wang³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Aberrant localization and over-expression of Ezrin have been reported to be implicated in cervical cancer (CC). Aberrant promoter methylation of some gene families may serve as potential diagnostic biomarkers for CC. In this study, we explored the correlation of promoter methylation of the Ezrin gene with the incidence and prognosis of CC. Methods: Cervical tissues from a total of 483 patients with CC were collected from the China-Japan Union Hospital of Jilin University. Samples were assigned into four groups accordingly to pathological diagnosis, namely the control group, the cervical intraepithelial neoplasia (CIN) I group, the CIN II-III group and the CC group. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed to detect the mRNA expression of Ezrin. Methylation-specific polymerase chain reaction (MSP) was used to detect the promoter methylation of the Ezrin gene. The Kaplan-Meier product-limit method and the log-rank analysis were used for survival analysis, the Cox regression analysis for the prognostic factors for CC, and the logistic regression analysis for the risk factors for the occurrence of CC. Results: The methylation rate of the Ezrin gene was correspondingly increased from the control, the CIN I, the CIN II-III to the CC groups. Over-expressed mRNA of Ezrin was determined in CC tissues. The mRNA expression of Ezrin was correlated with tumor size, lymphatic metastasis, pathological grade and clinical stage (FIGO). The risk factors for the occurrence of CC were the number of abortions and the promoter methylation of the Ezrin gene. Poor prognosis of CC correlated to lymphatic metastasis, higher pathological grade, higher FIGO stage and positive Ezrin promoter methylation. Conclusion: These findings indicate that promoter methylation of the Ezrin gene may play a crucial role in carcinogenesis, progression and prognosis of CC.

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Aberrant methylation of DACT1 and DACT2 are associated with tumor progression and poor prognosis in esophageal squamous cell carcinoma

Cited by 22 publications

References 35 publications

Effects of DACT1 methylation status on invasion and metastasis of nasopharyngeal carcinoma

Effects of DACT1 methylation status on invasion and metastasis of nasopharyngeal carcinoma

HPV‐related methylation‐based reclassification and risk stratification of cervical cancer

Promoter Methylation of Ezrin and its Impact on the Incidence and Prognosis of Cervical Cancer

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