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Current clinical analysis of the\n                      <jats:italic>HER2<\/jats:italic>\n                      status primarily relies on solid tumour biopsies low-suitable for continuous real-time monitoring needed for possible adjustment of the treatment, while serum tests targeting blood-circulating HER-2\/\n                      <jats:italic>neu<\/jats:italic>\n                      fragments often show conflicting tumour-serum relations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A cellulase-linked aptamer sandwich assay was used for detection of total urokinase plasminogen activator (uPA) and its different forms in serum of cancer patients and healthy individuals. Serum uPA levels were correlated with solid biopsy results and relevant clinical data extracted from electronic patient records, and FDG-PET\/CT scanning.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We show that serum uPA precisely stratifies patients with HER-2\/\n                      <jats:italic>neu<\/jats:italic>\n                      overexpressing (\n                      <jats:italic>HER2<\/jats:italic>\n                      +) and borderline-expressing cancers. Serum levels of total uPA 96.8% accurately informed about HER-2\/\n                      <jats:italic>neu<\/jats:italic>\n                      tumour status in a cohort of 100 patients, with a\n                      <jats:italic>HER2<\/jats:italic>\n                      +\/borderline expression cut-off value of 0.973\u2009ng\u2009mL\n                      <jats:sup>\u22121<\/jats:sup>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The established liquid biopsy test for serum uPA has potential for accurate diagnosis and staging of patients with\n                      <jats:italic>HER2<\/jats:italic>\n                      + and borderline-expressing cancers requiring further confirmatory (or rejection) testing.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41416-026-03471-5","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T17:19:31Z","timestamp":1779297571000},"page":"649-658","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Differentiating borderline HER2-expressing and HER2-positive cancers from other subtypes using serum urokinase plasminogen activator"],"prefix":"10.1038","volume":"135","author":[{"given":"Michael E. 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The current work is done independently, and the authors declare no competing financial interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"Blood samples from healthy volunteers and patients FDG-PET\/CT scanned on suspicion of breast, oesophagus and gastric cancers were collected at Aarhus University Hospital, Aarhus, Denmark. All subjects signed an informed consent form. The study was approved by the Regional Ethics Committee for Science in the Central Region of Jutland, Denmark, approval number 1-10-72-168-22. The performed research fully complies with the Helsinki Declaration (in its latest versions).","order":2,"name":"Ethics","label":"Ethical approval and consent to participate","group":{"name":"EthicsHeading","label":"Ethics"}}]}}