A blood-based polyamine signature associated with MEN1 duode
Duodenopancreatic neuroendocrine tumors (dpNETs) frequently occur in patients with Multiple Endocrine Neoplasia Type 1 (MEN1), and metastatic dpNET is the primary cause of disease-related mortality. There is a need for biomarkers that can identify patients with MEN1-related dpNETs that are at high risk of developing distant metastasis. Polyamines have tumor promoting roles in several cancer types. Researchers hypothesized that MEN1-dpNET-related disease progression is associated with elevated levels of circulating polyamines.

Through an international collaboration between MD Anderson Cancer Center (MDACC), the National Institutes of Health (NIH), and the University Medical Center Utrecht (UMCU), plasma polyamine levels were assessed using mass spectrometry in a total of 84 patients with MEN1 (20 with distant metastatic dpNETs (cases) and 64 with either indolent dpNETs or no dpNETs (controls)). A mouse model of MEN1-pNET, Men1 fl/flPdx1-Cre Tg, was used to test time-dependent changes in plasma polyamines associated with disease progression.

-- A 3-marker plasma polyamine signature (3MP: n-acetylputrescine, acetylspermidine, and diacetylspermidine) distinguished patients with metastatic dpNETs from controls in an initial set of plasmas from the three participating centers.

-- The fixed 3MP yielded an AUC of 0.84 with 66.7% sensitivity at 95% specificity for distinguishing cases from controls in an independent test set from MDACC.

-- In Men1 fl/flPdx1-Cre Tg mice, the 3MP was elevated early and remained high during disease progression.

Conclusively, these findings provide a basis for prospective testing of blood-based polyamines as a potential means for monitoring patients with MEN1 for harboring or developing aggressive disease.

Source: https://academic.oup.com/jcem/advance-article-abstract/doi/10.1210/clinem/dgab554/6329395?redirectedFrom=fulltext