{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:49:37Z","timestamp":1792028977343,"version":"4.4.0"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T00:00:00Z","timestamp":1669680000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81702717"],"award-info":[{"award-number":["81702717"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81902634"],"award-info":[{"award-number":["81902634"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2014A030310139"],"award-info":[{"award-number":["2014A030310139"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009330","name":"Medical Science and Technology Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["A2022084"],"award-info":[{"award-number":["A2022084"]}],"id":[{"id":"10.13039\/501100009330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aim<\/jats:title>\n                    <jats:p>Aberrant DNA methylation has been found in various cancer types including gastric cancer, yet the genome\u2010wide DNA methylation profile of gastric cardia cancer (GCC) remains unclear. Therefore, we aimed to profile the DNA methylation pattern of GCC and identify promising diagnostic epigenetic biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We investigated the genome\u2010wide DNA methylation pattern in eight pairs of GCC and adjacent normal tissues using Illumina 850K microarrays. Subsequently, bisulfite\u2010pyrosequencing and quantitative real\u2010time PCR were performed on eight pairs of GCC\u2010adjacent normal tissues for validation. Finally, we performed immunohistochemistry to examine ADHFE1 expression on 126 pairs of GCC\u2010adjacent normal samples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      DNA\u00a0methylome analysis showed global hypomethylation and local hypermethylation of promoter cytosine\u2010phosphate\u2010guanine (CpG) islands (CGIs) in GCC tissues compared with gastric cardia normal mucosa (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a02.2\u00a0\u00d7\u00a010\n                      <jats:sup>\u221216<\/jats:sup>\n                      ). Differential methylation analysis identified a total of 91 723 differentially\u2010methylated probes (DMPs), and the candidate gene with the largest average DNA methylation difference mapped to\n                      <jats:italic>ADHFE1<\/jats:italic>\n                      (mean \u0394\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u00a0=\u00a00.53). Subsequently, three DMPs in the\n                      <jats:italic>ADHFE1<\/jats:italic>\n                      promoter were validated by pyrosequencing. Notably,\u00a0the mean methylation level of the three candidate DMPs (\n                      <jats:italic>ADHFE1<\/jats:italic>\n                      _cg08090772,\n                      <jats:italic>ADHFE1<\/jats:italic>\n                      _cg19283840, and\n                      <jats:italic>ADHFE1<\/jats:italic>\n                      _cg20295442) was negatively associated with ADHFE1 mRNA expression level (Spearman rho\u00a0=\u00a0\u22120.64,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.01). Moreover, both mRNA (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0213) and protein (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001) expression of ADHFE1 were significantly decreased in GCCs compared with the adjacent normal tissues.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our results reveal DNA methylation aberrations in GCC and that\n                      <jats:italic>ADHFE1<\/jats:italic>\n                      gene DNA methylation contributes to the risk of GCC, thus providing novel mechanistic insights into gastric cardia cancer carcinogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jgh.16054","type":"journal-article","created":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T13:10:05Z","timestamp":1667826605000},"page":"290-300","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Genome\u2010wide DNA methylation profiling of gastric cardia cancer"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7014-9829","authenticated-orcid":false,"given":"Runhua","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Pathology Shantou University Medical College  Shantou China"},{"name":"Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology Shantou University Medical College  Shantou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanli","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Pathology Shantou University Medical College  Shantou 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