{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:04:17Z","timestamp":1787313857889,"version":"build-2736575974"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,2,28]],"date-time":"2021-02-28T00:00:00Z","timestamp":1614470400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Circulating tumor DNA (ctDNA) detected before surgery disappears after complete surgical resection of the cancer. Residual ctDNA indicates minimal residual disease (MRD), which is a cause of recurrence. The presence of long\u2010fragment circulating cell\u2010free DNA (cfDNA) or methylated cfDNA also implies the presence of cancer. In this study, we evaluated the prognostic value of cfDNA methylation and long\u2010fragment cfDNA concentration in gastric cancer patients undergoing curative surgery<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Ninety\u2010nine gastric cancer patients were included. Peripheral blood samples were collected before and 1 month after surgery. In patients administered chemotherapy, samples were collected before starting chemotherapy. qPCR was performed to detect long\u2010 and short\u2010fragment LINE\u20101. A plasma HELP (HpaII tiny fragment Enrichment by Ligation\u2010mediated PCR) assay to determine the concentration of HpaII small fragments was performed using ligation\u2010mediated PCR and HpaII was quantified as the HpaII:MspI ratio to detect methylation levels of cfDNA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Overall survival (OS) of patients with low methylation levels before starting treatment was significantly worse than that of patients with high methylation levels (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.006). In the 90 patients who underwent curative surgery, recurrence\u2010free survival (RFS) and OS of patients with low methylation levels before surgery were worse than those with high methylation levels (P=0.08 and\n                      <jats:italic>P<\/jats:italic>\n                      = 0.11, respectively). RFS and OS of patients with high concentrations of long\u2010fragment LINE\u20101 after surgery were significantly worse than those with low concentrations of long\u2010fragment LINE\u20101 (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.009,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.04).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Pre\u2010surgical low methylation levels of LINE\u20101 are a negative prognostic factor. Post\u2010surgical high concentrations of long\u2010fragment LINE\u20101 indicate MRD and a high risk of recurrence.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.3755","type":"journal-article","created":{"date-parts":[[2021,2,28]],"date-time":"2021-02-28T04:35:05Z","timestamp":1614486905000},"page":"2003-2012","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Methylation status and long\u2010fragment cell\u2010free DNA are prognostic biomarkers for gastric cancer"],"prefix":"10.1002","volume":"10","author":[{"given":"Kazuhide","family":"Ko","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal and Hepato\u2010Biliary\u2010Pancreatic Surgery Nippon Medical School Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshikazu","family":"Kananazawa","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and 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