Saudi Journal of Gastroenterology
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ORIGINAL ARTICLE
Year : 2022  |  Volume : 28  |  Issue : 6  |  Page : 456-465

Aberrant DNA methylation and expression of EYA4 in gastric cardia intestinal metaplasia


1 Department of Pathology, Shantou University Medical College, Shantou, P.R. China
2 Department of Gastroenterology, Shenzhen Second People's Hospital/The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, P.R. China
3 Department of Gastroenterology, Huiyang Sanhe Hospital, Huizhou, P.R. China
4 Department of Pathology, Shenzhen Second People's Hospital/The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, P.R. China
5 Department of Pathology, Shantou University Medical College; Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou, P.R. China

Correspondence Address:
Dr. Runhua Lin
Department of Pathology, Shantou University Medical College, No. 22, Xinling Road, Shantou 515041
P.R. China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/sjg.sjg_228_22

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Background: Intestinal metaplasia (IM) of the gastric cardia is an important premalignant lesion. However, there is limited information concerning its epidemiological and molecular features. Herein, we aimed to provide an overview of the epidemiological data for gastric cardiac IM and evaluate the role of EYA transcriptional coactivator and phosphatase 4 (EYA4) as an epigenetic biomarker for gastric cardiac IM. Methods: The study was conducted in the context of the gastric cardiac precancerous lesion program in southern China, which included 718 non-cancer participants, who undertook endoscopic biopsy and pathological examination in three endoscopy centers, between November 2018 and November 2021. Pyrosequencing and immunohistochemistry were performed to examine the DNA methylation status and protein expression level of EYA4. Results: Gastric cardiac IM presented in 14.1% (101/718) of participants and was more common among older (>50 years; 22.0% [95% CI: 17.8–26.8]) than younger participants (≤50 years; 6.7% [95% CI: 4.5–9.9]; P < 0.001). IM was more common in male participants (16.9% [95% CI: 13.2–21.3] vs. 11.3% [95% CI: 8.3–15.1]; P = 0.04). Pyrosequencing revealed that IM tissues exhibited significantly higher DNA methylation levels in EYA4 gene than normal tissues (P = 0.016). Further, the protein expression level of EYA4 was reduced in IM and absent in intraepithelial neoplasia tissues compared to normal tissues (P < 0.001). Conclusions: Detection rates of gastric cardiac IM increase with age and are higher in men. Our findings highlight the important role of promoter hypermethylation and downregulation of EYA4 in gastric cardiac IM development.


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