{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T20:17:28Z","timestamp":1787775448336,"version":"build-2784847793"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      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 (\n                      <jats:italic toggle=\"yes\">EYA4<\/jats:italic>\n                      ) as an epigenetic biomarker for gastric cardiac IM.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic toggle=\"yes\">EYA4<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Gastric cardiac IM presented in 14.1% (101\/718) of participants and was more common among older (&gt;50 years; 22.0% [95% CI: 17.8\u201326.8]) than younger participants (\u226450 years; 6.7% [95% CI: 4.5\u20139.9];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.001). IM was more common in male participants (16.9% [95% CI: 13.2\u201321.3] vs. 11.3% [95% CI: 8.3\u201315.1];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.04). Pyrosequencing revealed that IM tissues exhibited significantly higher DNA methylation levels in\n                      <jats:italic toggle=\"yes\">EYA4<\/jats:italic>\n                      gene than normal tissues (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.016). Further, the protein expression level of\n                      <jats:italic toggle=\"yes\">EYA4<\/jats:italic>\n                      was reduced in IM and absent in intraepithelial neoplasia tissues compared to normal tissues (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic toggle=\"yes\">EYA4<\/jats:italic>\n                      in gastric cardiac IM development.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/sjg.sjg_228_22","type":"journal-article","created":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T05:11:42Z","timestamp":1667538702000},"page":"456-465","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":4,"title":["Aberrant DNA methylation and expression of EYA4 in gastric cardia intestinal 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