{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:52:45Z","timestamp":1787727165101,"version":"build-2784847793"},"reference-count":43,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,5,30]],"date-time":"2020-05-30T00:00:00Z","timestamp":1590796800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","award":["16H06279"],"award-info":[{"award-number":["16H06279"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Formalin\u2010fixed paraffin\u2010embedded (FFPE) tissues used for routine pathological diagnosis are valuable for cancer genomic analysis; however, the association between mutation status derived from these specimens and prognosis in pancreatic ductal adenocarcinoma (PDAC) remains unclear. We analyzed 50 cancer\u2010related gene mutations including driver genes in PDAC, using next\u2010generation sequencing (NGS) to clarify the association between gene mutations and prognosis. DNA was extracted from FFPE tissues obtained from 74 patients with untreated resectable PDAC who underwent surgery at our institution between 2013 and 2018. Fifty of the 74 patients with DNA extracts from FFPE samples suitable for NGS were analyzed. The prevalence of driver gene mutations was as follows: 84% for <jats:italic>KRAS<\/jats:italic>, 62% for <jats:italic>TP53<\/jats:italic>, 32% for <jats:italic>SMAD4<\/jats:italic>, and 18% for <jats:italic>CDKN2A<\/jats:italic>. There were no cases of single <jats:italic>SMAD4<\/jats:italic> mutations; its rate of coincidence with <jats:italic>KRAS<\/jats:italic> or <jats:italic>TP53<\/jats:italic> mutations was 30% and 2%, respectively. The combination of <jats:italic>KRAS<\/jats:italic> and <jats:italic>SMAD4<\/jats:italic> mutations resulted in significantly shorter relapse\u2010free survival (RFS; median survival time [MST], 12.3 vs. 28.9\u00a0months, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.014) and overall survival (OS; MST, 22.3\u00a0months vs. not reached, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.048). On multivariate analysis, the combination of <jats:italic>KRAS<\/jats:italic> and <jats:italic>SMAD4<\/jats:italic> mutations was an independent prognostic factor for RFS (hazard ratio [HR] 4.218; 95% confidence interval [CI], 1.77\u201010.08; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.001) and OS (HR 6.730; 95% CI, 1.93\u201023.43; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.003). The combination of <jats:italic>KRAS<\/jats:italic> and <jats:italic>SMAD4<\/jats:italic> mutations in DNA obtained from FFPE tissues is an independent poor prognostic factor in PDAC.<\/jats:p>","DOI":"10.1111\/cas.14425","type":"journal-article","created":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T07:36:15Z","timestamp":1587454575000},"page":"2174-2182","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Combination of <i>KRAS<\/i> and <i>SMAD4<\/i> mutations in formalin\u2010fixed paraffin\u2010embedded tissues as a biomarker for pancreatic cancer"],"prefix":"10.1111","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6946-280X","authenticated-orcid":false,"given":"Takahiro","family":"Yokose","sequence":"first","affiliation":[{"name":"Department of Surgery Keio University School of Medicine Tokyo 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