{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T20:35:52Z","timestamp":1774038952433,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,5,25]],"date-time":"2016-05-25T00:00:00Z","timestamp":1464134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Helicobacter"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; aims<\/jats:title><jats:p>Gastric cancer has familial clustering in incidence, and the familial relatives of gastric cancer sufferers are prone to have spasmolytic polypeptide\u2010expressing metaplasia (SPEM), and intestinal metaplasia (IM) after <jats:italic>H. pylori<\/jats:italic> infection. This study tested whether serum pepsinogen I\/II and trefoil factor family (TFF) proteins can predict SPEM or IM in the <jats:italic>H. pylori<\/jats:italic>\u2010infected relatives of patients with gastric cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We prospectively enrolled 119 <jats:italic>H. pylori<\/jats:italic>\u2010infected relatives of gastric cancer patients of noncardiac gastric cancer patients, who then received panendoscopy to obtain gastric biopsy to define the presence of corpus gastritis index (CGI), SPEM, and IM. The advanced SPEM in histology was defined by TFF2 immunohistochemistry. Each patient also had checkups of serum TFF2, TFF3<jats:italic>,<\/jats:italic> and pepsinogen I\/II by enzyme\u2010linked immunosorbent assay (ELISA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The 119 <jats:italic>H. pylori<\/jats:italic>\u2010infected relatives included 61 with SPEM, and 34 with IM. The presence of either IM or SPEM was not related to the serum TFF2, TFF3, and pepsinogen I\/II levels (<jats:italic>p<\/jats:italic> &gt; .05). Serum TFF2 levels were higher in relatives with CGI who also had advanced SPEM (<jats:italic>p<\/jats:italic> = .032). For relatives without CGI, the elevated serum TFF2 levels correlated with higher <jats:italic>H. pylori<\/jats:italic> density and more severe gastritis in antrum (<jats:italic>p<\/jats:italic> = .001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The serum TFF2 level cannot predict SPEM or IM in <jats:italic>H. pylori\u2010<\/jats:italic>infected relatives of patients with gastric cancer. For <jats:italic>H. pylori\u2010<\/jats:italic>infected relatives with CGI, serum TFF2 levels may predict the advanced severity of SPEM. Elevated serum TFF2 levels may indicate severe <jats:italic>H. pylori<\/jats:italic>\u2010related inflammation, at risk of development or progression of SPEM in relatives without CGI.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hel.12320","type":"journal-article","created":{"date-parts":[[2016,5,25]],"date-time":"2016-05-25T10:36:24Z","timestamp":1464172584000},"source":"Crossref","is-referenced-by-count":16,"title":["Serum Level of Trefoil Factor 2 can Predict the Extent of Gastric Spasmolytic Polypeptide\u2010Expressing Metaplasia in the <i>H. pylori\u2010<\/i>Infected Gastric Cancer Relatives"],"prefix":"10.1111","volume":"22","author":[{"given":"Hsin\u2010Yu","family":"Kuo","sequence":"first","affiliation":[{"name":"Institute of Clinical Medicine National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan Taiwan"},{"name":"Department of Internal Medicine National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei\u2010Lun","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi\u2010Chun","family":"Yeh","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu\u2010Ching","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan Taiwan"},{"name":"Department of Internal Medicine Tainan Hospital Tainan Taiwan"},{"name":"Department of Health Executive Yuan Tainan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chung\u2010Tai","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan Taiwan"},{"name":"Department of Internal Medicine National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsiu\u2010Chi","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsiao\u2010Bai","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathology National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan Taiwan"},{"name":"Department of Pathology Ton\u2010Yen General Hospital Hsin\u2010chu Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng\u2010Chang","family":"Lu","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan Taiwan"},{"name":"Department of Pathology National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bor\u2010Shyang","family":"Sheu","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan Taiwan"},{"name":"Department of Internal Medicine National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,5,25]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"3554","article-title":"A human model of gastric carcinogenesis","volume":"48","author":"Correa P","year":"1988","journal-title":"Cancer Res"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.04.023"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2012-302401"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.1996.v110.pm8536852"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(00)70412-4"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1203"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2003.10.019"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2007.10.003"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199708)182:4<404::AID-PATH875>3.0.CO;2-0"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.08.043"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)61121-2"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/hupa.2002.124907"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.05.040"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-011-0396-8"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-230X-14-74"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(00)70410-0"},{"key":"e_1_2_6_18_1","first-page":"5245","article-title":"Higher gastric cycloxygenase\u20102 expression and precancerous change in Helicobacter pylori\u2010infected relatives of gastric cancer patients","volume":"9","author":"Sheu BS","year":"2003","journal-title":"Clin Cancer Res"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2012.05111.x"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1291491"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.12291"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2013-304531"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2015-309252"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.01.071"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwj088"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:DDAS.0000030091.92379.91"},{"key":"e_1_2_6_27_1","first-page":"119","article-title":"Serum anti\u2010Helicobacter pylori IgG antibodies and pepsinogens A and C as serological markers of chronic atrophic gastritis","volume":"2","author":"Sitas F","year":"1993","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2007.11.016"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10120-012-0185-y"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(95)90340-2"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117332"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(95)90014-4"},{"key":"e_1_2_6_33_1","first-page":"783","article-title":"Trefoil peptides are early markers of gastrointestinal maturation in the rat","volume":"42","author":"Familari M","year":"1998","journal-title":"Int J Dev Biol"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.070249"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10120-009-0527-6"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.01.043"}],"container-title":["Helicobacter"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhel.12320","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhel.12320","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hel.12320","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T19:44:49Z","timestamp":1696275889000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hel.12320"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,25]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,2]]}},"alternative-id":["10.1111\/hel.12320"],"URL":"https:\/\/doi.org\/10.1111\/hel.12320","archive":["Portico"],"relation":{},"ISSN":["1083-4389","1523-5378"],"issn-type":[{"value":"1083-4389","type":"print"},{"value":"1523-5378","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,25]]},"article-number":"e12320"}}