{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T04:32:56Z","timestamp":1785213176714,"version":"3.55.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T00:00:00Z","timestamp":1705968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Innovative Team Grand of Guangdong Department of Education","award":["2020KCXTD033"],"award-info":[{"award-number":["2020KCXTD033"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073290"],"award-info":[{"award-number":["82073290"]}],"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":["81772997"],"award-info":[{"award-number":["81772997"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shantou Science and Technology Bureau","award":["210712186880511"],"award-info":[{"award-number":["210712186880511"]}]},{"name":"Shantou Science and Technology Bureau","award":["[2022]88-44"],"award-info":[{"award-number":["[2022]88-44"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Intestinal metaplasia (IM) and intraepithelial neoplasia (IEN) are considered precursors of gastric cardia cancer (GCC). Here, we investigated the histopathologic and molecular profiles of precancerous gastric cardia lesions (PGCLs) and biomarkers for risk stratification of gastric cardia IM.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a hospital-based evaluation (n\u2009=\u20094578) for PGCL profiles in high-incidence and non-high-incidence regions for GCC in China. We next performed 850K methylation arrays (n\u2009=\u200942) and RNA-seq (n\u2009=\u200944) in tissues with PGCLs. We then examined the protein expression of candidate biomarker using immunohistochemistry.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of the 4578 participants, 791 were diagnosed with PGCLs (600 IM, 62 IM with IEN, and 129 IEN). We found that individuals from high-incidence regions (26.7%) were more likely to develop PGCLs than those from non-high-incidence areas (13.5%). DNA methylation and gene expression alterations, indicated by differentially methylated probes (DMPs) and differentially expressed genes (DEGs), exhibited a progressive increase from type I IM (DMP\u2009=\u2009210, DEG\u2009=\u200924), type II IM (DMP\u2009=\u20093402, DEG\u2009=\u2009129), to type III IM (DMP\u2009=\u20093735, DEG\u2009=\u2009328), peaking in IEN (DMP\u2009=\u200947\u200a373, DEG\u2009=\u20092278). Three DEGs with aberrant promoter methylation were identified, shared exclusively by type III IM and IEN. Of these DEGs, we found that OLFM4 expression appears in IMs and increases remarkably in IENs (P\u2009&amp;lt;\u2009.001).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We highlight that type III IM and IEN share similar epigenetic and transcriptional features in gastric cardia and propose biomarkers with potential utility in risk prediction.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jnci\/djad244","type":"journal-article","created":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T10:48:16Z","timestamp":1706006896000},"page":"681-693","source":"Crossref","is-referenced-by-count":10,"title":["Genome-wide DNA methylation and transcriptomic patterns of precancerous gastric cardia lesions"],"prefix":"10.1093","volume":"116","author":[{"given":"Xiaoqi","family":"Liao","sequence":"first","affiliation":[{"name":"Department of Pathology, Shantou University Medical College , Shantou, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runhua","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pathology, Shantou University Medical College , Shantou, People\u2019s Republic of China"},{"name":"Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College , Shantou, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Shantou University Medical College , Shantou, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongping","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Pathology, Shantou University Medical College , Shantou, People\u2019s Republic of China"},{"name":"Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College , Shantou, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohui","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shenzhen Second People\u2019s Hospital\/The First Affiliated Hospital of Shenzhen University Health Science Center , Shenzhen, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songqin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Jieyang People\u2019s Hospital , Jieyang, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohua","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Huiyang Sanhe Hospital , Huizhou, People\u2019s Republic of 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