{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T13:55:02Z","timestamp":1789134902279,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T00:00:00Z","timestamp":1656460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA138313"],"award-info":[{"award-number":["P30 CA138313"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Elevated serum carcinoembryonic antigen (CEA) is used to identify \u201ctreatment emergent\u201d forms of castration\u2010resistant prostate cancer (CRPC) such as aggressive variant prostate cancer (AVPC). However, its individual utility as a prognostic marker and the genetic alterations associated with its expression have not been extensively studied in CRPC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study retrospectively analyzed clinical outcomes and circulating tumor DNA profiles in 163 patients with CRPC and elevated or normal serum CEA. These same patients were then classified as AVPC or non\u2010AVPC and compared to determine the uniqueness of CEA\u2010associated\u00a0gene alterations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Patients with elevated CEA demonstrated higher rates of liver metastasis (37.5% vs. 19.1%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.02) and decreased median overall survival from CRPC diagnosis (28.7 vs. 73.2 mo,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). In addition, patients with elevated CEA were more likely to harbor copy number amplifications (CNAs) in\n                      <jats:italic>AR, PIK3CA, MYC, BRAF, CDK6, MET, CCNE1, KIT, RAF1<\/jats:italic>\n                      , and\n                      <jats:italic>KRAS<\/jats:italic>\n                      . Based on variant allele frequency we also defined \u201cclonal\u201d single\u2010nucleotide variants (SNVs) thought to be driving disease progression in each patient and found that CEA expression was negatively correlated with clonal\n                      <jats:italic>AR<\/jats:italic>\n                      SNVs and positively correlated with clonal\n                      <jats:italic>TP53<\/jats:italic>\n                      SNVs. Of these genetic associations, only the increases in clonal\n                      <jats:italic>TP53<\/jats:italic>\n                      SNVs and\n                      <jats:italic>KRAS<\/jats:italic>\n                      amplifications were recapitulated among patients with AVPC when compared to patients without AVPC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Together these findings suggest that CEA expression in CRPC is associated with aggressive clinical behavior and gene alterations distinct from those in AVPC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pros.24400","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T06:56:32Z","timestamp":1656485792000},"page":"1264-1272","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Elevated serum CEA is associated with liver metastasis and distinctive circulating tumor DNA alterations in patients with castration\u2010resistant prostate cancer"],"prefix":"10.1002","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1849-2555","authenticated-orcid":false,"given":"Alexander W.","family":"Bray","sequence":"first","affiliation":[{"name":"Department of Medicine Medical University of South Carolina Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences Medical University of South Carolina Charleston South Carolina USA"},{"name":"Hollings Cancer Center Medical University of South Carolina Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pannaga","family":"Malalur","sequence":"additional","affiliation":[{"name":"The Ohio State University Wexner Medical Center Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leylah M.","family":"Drusbosky","sequence":"additional","affiliation":[{"name":"Guardant Health, Inc Redwood City California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore S.","family":"Gourdin","sequence":"additional","affiliation":[{"name":"Department of Medicine Medical University of South Carolina Charleston South Carolina USA"},{"name":"Hollings Cancer Center Medical University of South Carolina Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth G.","family":"Hill","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences Medical University of South Carolina Charleston South Carolina USA"},{"name":"Hollings Cancer Center Medical University of South Carolina Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B.","family":"Lilly","sequence":"additional","affiliation":[{"name":"Department of Medicine Medical University of South Carolina Charleston South Carolina USA"},{"name":"Hollings Cancer Center Medical University of South Carolina Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-540-40901-4_1"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euf.2016.11.012"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-3791"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-3309"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-1259"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12123792"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0140712"},{"key":"e_1_2_8_9_1","unstructured":"Network NCC. 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