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DNA methylation profiling identifies epigenetic signatures of early gastric cancer

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Abstract

Research on the DNA methylation status of gastric cancer (GC) has primarily focused on identifying invasive GC to develop biomarkers for diagnostic. However, DNA methylation in noninvasive GC remains unclear. We conducted a comprehensive DNA methylation profiling study of differentiated-type intramucosal GCs (IMCs). Illumina 850K microarrays were utilized to assess the DNA methylation profiles of formalin-fixed paraffin-embedded tissues from eight patients who were Epstein-Barr virus-negative and DNA mismatch repair proficient, including IMCs and paired adjacent nontumor mucosa. Gene expression profiling microarray data from the GEO database were analyzed via bioinformatics to identify candidate methylation genes. The final validation was conducted using quantitative real-time PCR, the TCGA methylation database, and single-sample gene set enrichment analysis (GSEA). Genome-wide DNA methylation profiling revealed a global decrease in methylation in IMCs compared with nontumor tissues. Differential methylation analysis between IMCs and nontumor tissues identified 449 differentially methylated probes, with a majority of sites showing hypomethylation in IMCs compared with nontumor tissues (66.1% vs 33.9%). Integrating two RNA-seq microarray datasets, we found one hypomethylation-upregulated gene: eEF1A2, overlapped with our DNA methylation data. The mRNA expression of eEF1A2 was higher in twenty-four IMC tissues than in their paired adjacent nontumor tissues. GSEA indicated that the functions of eEF1A2 were associated with the development of IMCs. Furthermore, TCGA data indicated that eEF1A2 is hypomethylated in advanced GC. Our study illustrates the implications of DNA methylation alterations in IMCs and suggests that aberrant hypomethylation and high mRNA expression of eEF1A2 might play a role in IMCs development.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

This work was supported by Innovation Technology Project, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China (No. 21kcjj-9).

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Authors and Affiliations

  1. Department of Pathology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China

    Zhongyue Shi, Xinmeng Guo, Xiumei Hu, Ruiqi Li, Xue Li, Jun Lu, Mulan Jin & Xingran Jiang

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  1. Zhongyue Shi
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  2. Xinmeng Guo
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Contributions

ZS, MJ, and XJ designed the study. ZS, XG, and RL completed the experiment. ZS, XH, JL, and XL collected the data. ZS, XH, JL, and XL analyzed and interpreted the data. ZS, XJ, and MJ prepared the manuscript. All authors contributed to the article and approved the submitted version.

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Correspondence to Mulan Jin or Xingran Jiang.

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Approval of the research protocol by the local ethics committee (Beijing Chao-Yang Hospital, Capital Medical University, NO. 2020-KE-323).

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Shi, Z., Guo, X., Hu, X. et al. DNA methylation profiling identifies epigenetic signatures of early gastric cancer. Virchows Arch 484, 687–695 (2024). https://doi.org/10.1007/s00428-024-03765-0

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