Specific DNA methylation markers in the diagnosis and prognosis of esophageal cancer

Li, Dapeng; Zhang, Lei; Liu, Yupeng; Sun, Hongru; Onwuka, Justina Ucheojor; Zhao, Zhenjuan; Tian, Wenjing; Xu, Jing; Zhao, Yashuang; Xu, Hongyu

doi:10.18632/aging.102569

Cited by 45 publications

(45 citation statements)

References 35 publications

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“…Indeed, in treatmentnaïve tumors, the three selected genes disclosed different methylation levels among ESCC and EA, variably comparing to normal esophageal tissue samples. Differential methylation patterns between ESCC and EA have been previously reported and are in line with our results (31,32). In particular, available data support the value of identi cation speci c ESCC methylation panels to enable early detection (16,33,34).…”

Section: Discussionsupporting

confidence: 92%

A DNA Methylation-based Test for Esophageal Cancer Detection

Salta

Macedo-Silva

Miranda‐Gonçalves

et al. 2020

Preprint

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Background Esophageal cancer (ECa) is the 7th most incident cancer and the 6th leading cause of cancer-related death. Most patients are diagnosed with locally advanced or metastatic disease, enduring poor survival. Biomarkers enabling early cancer detection may improve patient management, treatment effectiveness and survival are urgently needed. In this context, epigenetic-based biomarkers such as DNA methylation are potential candidates. Methods Herein, we sought to identify and validate DNA methylation-based biomarkers for early detection and prediction of response to therapy in ECa patients. Promoter methylation levels were assessed in a series of treatment-naïve ECa, post-neoadjuvant treatment ECa and normal esophagus tissues, using quantitative methylation-specific PCR for COL14A1, GPX3, and ZNF569. Results ZNF569 methylation (ZNF569me) levels significantly differed between ECa and normal samples. Moreover, COL14A1 methylation (COL14A1me) and GPX3 methylation (GPX3me) levels discriminated adenocarcinomas and squamous cell carcinomas, respectively, from normal samples. COL14A1me & ZNF569me accurately identified adenocarcinomas (82.29%) whereas GPX3me & ZNF569me identified squamous cell carcinomas with 81.73% accuracy. Furthermore, ZNF569me and GPX3me levels significantly differed between normal and pre-treated ECa. Conclusion The biomarker potential of a specific panel of methylated genes for ECa was confirmed. These might prove useful for early detection and might allow for identification of minimal residual disease after adjuvant therapy.

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Section: Discussionsupporting

confidence: 92%

A DNA Methylation-based Test for Esophageal Cancer Detection

Salta

Macedo-Silva

Miranda‐Gonçalves

et al. 2020

Preprint

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“…ESCC and EA displayed different cancer-speci c methylation patterns. Accordingly, differential methylation patterns have been previously reported between ESCC and EA (38,39). Indeed, in treatmentnaïve tumors, the three selected genes disclosed different methylation levels among ESCC and EA, variably comparing to normal esophageal tissue samples.…”

Section: Discussionmentioning

confidence: 83%

A DNA Methylation-based Test for Esophageal Cancer Detection

Salta

Macedo-Silva

Miranda‐Gonçalves

et al. 2020

Preprint

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Background: Esophageal cancer (ECa) is the 7 th most incident cancer and the 6 th leading cause of cancer-related death. Most patients are diagnosed with locally advanced or metastatic disease, enduring poor survival. Biomarkers enabling early cancer detection may improve patient management, treatment effectiveness, and survival, are urgently needed. In this context, epigenetic-based biomarkers such as DNA methylation are potential candidates. Methods: Herein, we sought to identify and validate DNA methylation-based biomarkers for early detection and prediction of response to therapy in ECa patients. Promoter methylation levels were assessed in a series of treatment-naïve ECa, post-neoadjuvant treatment ECa, and normal esophagus tissues, using quantitative methylation-specific PCR for COL14A1 , GPX3, and ZNF569 . Results: ZNF569 methylation ( ZNF569me) levels significantly differed between ECa and normal samples ( p <0.001). Moreover, COL14A1 methylation ( COL14A1me) and GPX3 methylation ( GPX3me) levels discriminated adenocarcinomas and squamous cell carcinomas, respectively, from normal samples ( p =0.002 and p =0.009, respectively). COL14A1me & ZNF569me accurately identified adenocarcinomas (82.29%) whereas GPX3me & ZNF569me identified squamous cell carcinomas with 81.73% accuracy. Furthermore, ZNF569me and GPX3me levels significantly differed between normal and pre-treated ECa. Conclusion: The biomarker potential of a specific panel of methylated genes for ECa was confirmed. These might prove useful for early detection and might allow for the identification of minimal residual disease after adjuvant therapy.

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“…Plasma samples of patients suspected of having ESCC might be collected and analyzed for these hypermethylation events. 26,27 DNA methylation can alter the ability of transcription factors to bind DNA and regulate gene expression. 21,28,29 Dong et al 21 revealed that the hypermethylation within the proximal promoter of ZNF667-AS1 or ZNF667 influenced the binding ability of transcription factor E2F1 binding and the following transcriptional activation and expression of them.…”

Section: Discussionmentioning

confidence: 99%

Multiomic Analysis of Methylation and Transcriptome Reveals a Novel Signature in Esophageal Cancer

Jin¹,

Miao²

2020

Dose-Response

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Background: Epigenetic alterations have been shown to lead to human carcinogenesis. The aim of this study was to perform an integrative analysis to develop an epigenetic signature to predict overall survival (OS) of esophageal cancer. Methods: DNA methylation and messenger RNA expression data of esophageal cancer samples were downloaded from The Cancer Genome Atlas database and were incorporated and analyzed using an R package MethylMix. Functional enrichment analysis of the methylation-related differentially expressed genes (DEGs) was performed. Epigenetic signature and nomogram associated with the OS of esophageal cancer were established by the multivariate Cox model. Results: A total of 71 methylation-related DEGs were identified. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that these genes were involved in the biological process related to the initiation and progression of esophageal cancer. Two-gene (FAM24B and FAM200A) risk signature for OS was developed by multivariate Cox analysis, of which had high accuracy. The signature is independent of clinicopathological variables and indicated better predictive power than other clinicopathological variables. Moreover, we developed a novel prognostic nomogram based on risk score and 3 clinicopathological factors. Conclusions: Our study indicated possible methylation-related DEGs and established an epigenetic signature, which may provide novel insights for understanding the pathogenesis of esophageal cancer.

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Specific DNA methylation markers in the diagnosis and prognosis of esophageal cancer

Cited by 45 publications

References 35 publications

A DNA Methylation-based Test for Esophageal Cancer Detection

A DNA Methylation-based Test for Esophageal Cancer Detection

A DNA Methylation-based Test for Esophageal Cancer Detection

Multiomic Analysis of Methylation and Transcriptome Reveals a Novel Signature in Esophageal Cancer

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