{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:20:54Z","timestamp":1784557254322,"version":"3.55.0"},"reference-count":0,"publisher":"Bioscientifica","issue":"11","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,11,1]]},"abstract":"\n Pheochromocytomas and paragangliomas (PHEOs\/PGLs) represent diagnostically challenging and complex neuroendocrine tumors (NETs). Current biomarker tests for PHEOs\/PGLs are technically complex or limited. We assessed the diagnostic utility of a NET-specific 51-marker gene blood assay (NETest) in patients with PHEOs\/PGLs (\n n<\/jats:italic>\n \u2009= 81), including ten pediatric patients, and age-\/gender-matched controls (\n n<\/jats:italic>\n \u2009= 142) using a prospective case:control (1:2) analysis. mRNA was measured (qPCR), and results were scaled from 0 to 100 (upper limit of normal < 20). Receiver operating curve (ROC) and non-parametric (Mann\u2013Whitney) tests were used for analyses (two-tailed). All data are presented as mean \u00b1\n s.e.m<\/jats:sc>\n . NETest accuracy for PHEO\/PGL diagnosis was 100%. PHEO\/PGL scores were 70 \u00b1 3 vs 8.5 \u00b1 1 in controls (\n P<\/jats:italic>\n \u2009< 0.0001), and ROC analysis was 0.99 \u00b1 0.004 (\n P<\/jats:italic>\n \u2009< 0.0001). Diagnostic metrics were 94% accurate, 100% sensitive, and 92% specific. Imaging correlation with\n 68<\/jats:sup>\n Ga-PET-SSA was 100%. NETest levels in PHEOs (\n n<\/jats:italic>\n \u2009= 26) were significantly (\n P<\/jats:italic>\n \u2009< 0.0001) elevated (83 \u00b1 4) vs 66 \u00b1 4 in PGLs (\n n<\/jats:italic>\n \u2009= 40) and mixed PHEOs\/PGLs (\n n<\/jats:italic>\n \u2009= 5: 37 \u00b1 3). Adrenal-derived tumors (\n n<\/jats:italic>\n \u2009= 30) exhibited higher scores (76 \u00b1 5) than extra-adrenal-derived tumors (66 \u00b1 4,\n P<\/jats:italic>\n \u2009< 0.05). Cluster 2 tumors exhibited significantly (\n P<\/jats:italic>\n \u2009= 0.034) elevated NETest levels (\n n<\/jats:italic>\n \u2009= 4: 92 \u00b1 2) vs cluster 1 tumors (\n n<\/jats:italic>\n \u2009= 35: 69 \u00b1 4). Regulatory pathway analysis identified elevated RAS-RAF, metastatic, pluripotential, neural and secretory gene cluster levels (\n P<\/jats:italic>\n \u2009< 0.05) in PHEOs compared to PGLs. Cluster 2 PPGLs exhibited elevated (\n P<\/jats:italic>\n \u2009= 0.046) levels of growth factor signaling genes compared to cluster 1. The PHEOs\/PGLs in the pediatric cohort (\n n<\/jats:italic>\n \u2009= 10) were all NETest-positive (81 \u00b1 8) and exhibited a gene expression profile spectrum analogous to adults. Circulating NET transcript analysis identifies PHEOs\/PGLs with 100% efficacy and is likely to have clinical utility in the diagnosis and management of PHEO\/PGL patients.\n <\/jats:p>","DOI":"10.1530\/erc-21-0216","type":"journal-article","created":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T11:50:43Z","timestamp":1631533843000},"page":"731-744","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":12,"title":["A novel liquid biopsy (NETest) identifies paragangliomas and pheochromocytomas with high accuracy"],"prefix":"10.1530","volume":"28","author":[{"given":"Karel","family":"Pacak","sequence":"first","affiliation":[{"name":"1Section of Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Kidd","sequence":"additional","affiliation":[{"name":"2WREN Laboratories, Branford, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Meuter","sequence":"additional","affiliation":[{"name":"1Section of Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irvin M","family":"Modlin","sequence":"additional","affiliation":[{"name":"3Gastroenterological and Endoscopic Surgery, Yale University School of Medicine, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Endocrine-Related Cancer"],"original-title":[],"link":[{"URL":"https:\/\/erc.bioscientifica.com\/view\/journals\/erc\/28\/11\/ERC-21-0216.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/erc.bioscientifica.com\/downloadpdf\/journals\/erc\/28\/11\/ERC-21-0216.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:56:07Z","timestamp":1784555767000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/erc\/article\/28\/11\/731-744\/25472"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,1]]},"references-count":0,"journal-issue":{"issue":"11"},"URL":"https:\/\/doi.org\/10.1530\/erc-21-0216","relation":{},"ISSN":["1351-0088","1479-6821"],"issn-type":[{"value":"1351-0088","type":"print"},{"value":"1479-6821","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,1]]}}}