Multi-omic characterization of genome-wide abnormal DNA methylation reveals diagnostic and prognostic markers for esophageal squamous-cell carcinoma

Xi, Yuanzhe; Lin, Yuan; Guo, Wenjia; Wang, Xinyu; Zhao, Hengqiang; Miao, Chuanwang; Liu, Weiling; Liu, Yachen; Liu, Tianyuan; Luo, Yingying; Fan, Wenyi; Ai, Lin; Chen, Yamei; Sun, Yanxia; Ma, Yanning; Niu, Xiangjie; Zhong, Ce; Tan, Wen; Zhou, Meng; Su, Jianzhong; Wu, Chen; Lin, Dongxin

doi:10.1038/s41392-022-00873-8

Cited by 34 publications

(25 citation statements)

References 78 publications

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“…Although hypermethylation events of the two genes were rarely reported in ESCC by previous studies, they have been extensively studied in other cancer types, especially in breast cancer [39,40]. Interestingly, in a recently published study, researchers have investigated the potential of HOXC10 as a diagnostic marker for ESCC [41]. Using the WGBS technology, they identified the hypermethylated HOXC10 in their cohort, which is consistent with the findings of this study.…”

Section: Discussionsupporting

confidence: 87%

Genome-wide methylation profiling identify hypermethylated HOXL subclass genes as potential markers for esophageal squamous cell carcinoma detection

Xia

Zhao

et al. 2022

Preprint

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BackgroundNumerous studies have revealed aberrant DNA methylation in esophageal squamous cell carcinoma (ESCC). However, they often focused on the partial genome, which resulted in an inadequate understanding of the shaped methylation features and the lack of available methylation markers for this disease.MethodsThe current study investigated the methylation profiles between ESCC and paired normal samples using whole-genome bisulfite sequencing (WGBS) data and obtained a group of differentially methylated CpGs (DMC), differentially methylated regions (DMR), and differentially methylated genes (DMG). The DMGs were then verified in independent datasets and Sanger sequencing in our custom samples. Finally, we attempted to evaluate the performance of these genes as methylation markers for the classification of ESCC and multiple cancer types.ResultsWe obtained 438,558 DMCs, 15,462 DMRs, and 1,568 DMGs. The four significantly enriched gene families of DMGs were CD molecules, NKL subclass, HOXL subclass, and Zinc finger C2H2-type. The HOXL subclass homeobox genes were observed extensively hypermethylated in ESCC and nine other cancer types. The HOXL-score estimated by HOXC10 and HOXD1 methylation showed good ability in discriminating ESCC from normal samples, while the methylation of GSX1 displayed potential utility for pan-cancer detection.ConclusionsWe observed widespread hypomethylation events in ESCC, and the hypermethylated HOXL subclass homeobox genes presented promising applications for the early detection of multiple cancer types.

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Section: Discussionsupporting

confidence: 87%

Genome-wide methylation profiling identify hypermethylated HOXL subclass genes as potential markers for esophageal squamous cell carcinoma detection

Xia

Zhao

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Although hypermethylation events of the two genes are rarely reported in ESCC by previous studies, they have been extensively studied in other cancer types, especially in breast cancer [ 40 , 41 ]. Interestingly, in a recently published study, researchers have investigated the potential of HOXC10 as a diagnostic marker for ESCC [ 42 ]. Using the WGBS technology, they identified the hypermethylated HOXC10 in their cohort, which is consistent with the findings of this study.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide methylation profiling identify hypermethylated HOXL subclass genes as potential markers for esophageal squamous cell carcinoma detection

Xia

Zhao

et al. 2022

BMC Med Genomics

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Background Numerous studies have revealed aberrant DNA methylation in esophageal squamous cell carcinoma (ESCC). However, they often focused on the partial genome, which resulted in an inadequate understanding of the shaped methylation features and the lack of available methylation markers for this disease. Methods The current study investigated the methylation profiles between ESCC and paired normal samples using whole-genome bisulfite sequencing (WGBS) data and obtained a group of differentially methylated CpGs (DMC), differentially methylated regions (DMR), and differentially methylated genes (DMG). The DMGs were then verified in independent datasets and Sanger sequencing in our custom samples. Finally, we attempted to evaluate the performance of these genes as methylation markers for the classification of ESCC. Results We obtained 438,558 DMCs, 15,462 DMRs, and 1568 DMGs. The four significantly enriched gene families of DMGs were CD molecules, NKL subclass, HOXL subclass, and Zinc finger C2H2-type. The HOXL subclass homeobox genes were observed extensively hypermethylated in ESCC. The HOXL-score estimated by HOXC10 and HOXD1 methylation, whose methylation status were then confirmed by sanger sequencing in our custom ESCC samples, showed good ability in discriminating ESCC from normal samples. Conclusions We observed widespread hypomethylation events in ESCC, and the hypermethylated HOXL subclass homeobox genes presented promising applications for the early detection of esophageal squamous cell carcinoma.

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“…Studies have shown that the DNA methylation that occurs here is highly correlated with the carcinogenesis of esophageal cancer. Specifically, during the carcinogenesis of esophageal cancer, altered DNA methylation status in CpG islands can lead to increased chromosomal rotation and silencing and loss of expression of oncogenes, leading to tumour growth ( Xi et al, 2022 ). A variety of related gene methylations have been examined in esophageal cancer, such as p16, E-cadherin, DNMT1 and MTHFR.…”

Section: Dna Methylation and Esophageal Cancermentioning

confidence: 99%

Epigenetic modifications in esophageal cancer: An evolving biomarker

Liu

Zhao²,

Chen³

et al. 2023

Front. Genet.

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Esophageal cancer is a widespread cancer of the digestive system that has two main subtypes: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EA). In the diverse range of cancer therapy schemes, the side effects of conventional treatments remain an urgent challenge to be addressed. Therefore, the pursuit of novel drugs with multiple targets, good efficacy, low side effects, and low cost has become a hot research topic in anticancer therapy. Based on this, epigenetics offers an attractive target for the treatment of esophageal cancer, where major mechanisms such as DNA methylation, histone modifications, non-coding RNA regulation, chromatin remodelling and nucleosome localization offer new opportunities for the prevention and treatment of esophageal cancer. Recently, research on epigenetics has remained at a high level of enthusiasm, focusing mainly on translating the basic research into the clinical setting and transforming epigenetic alterations into targets for cancer screening and detection in the clinic. With the increasing emergence of tumour epigenetic markers and antitumor epigenetic drugs, there are also more possibilities for anti-esophageal cancer treatment. This paper focuses on esophageal cancer and epigenetic modifications, with the aim of unravelling the close link between them to facilitate precise and personalized treatment of esophageal cancer.

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Multi-omic characterization of genome-wide abnormal DNA methylation reveals diagnostic and prognostic markers for esophageal squamous-cell carcinoma

Cited by 34 publications

References 78 publications

Genome-wide methylation profiling identify hypermethylated HOXL subclass genes as potential markers for esophageal squamous cell carcinoma detection

Genome-wide methylation profiling identify hypermethylated HOXL subclass genes as potential markers for esophageal squamous cell carcinoma detection

Genome-wide methylation profiling identify hypermethylated HOXL subclass genes as potential markers for esophageal squamous cell carcinoma detection

Epigenetic modifications in esophageal cancer: An evolving biomarker

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