Protein signatures associated with distant metastatic MEN1-related dpNETS. (A) Volcano plot showing differential circulating proteins in patients with metastatic MEN1-related dpNETs (Cases; n = 14) compared to MEN1 patients with indolent dpNETs and without distant or regional metastases (Control-1; n = 28) or MEN1 patients without dpNETs (Control-2; n = 14). Orange nodes represent those proteins that were statistically significantly (raw P < 0.05) elevated in cases compared to controls; blue nodes represented proteins that are statistically significantly decreased. Horizonal dashed line shows raw P-value threshold of 0.05. P-values were determined by 2-sided Student T-test. (B) Ingenuity pathway analysis of the 187 proteins elevated in case plasmas revealed cancer, neurological disease, organismal injury, and abnormalities and endocrine system disorders among top predicted diseases. (C) Dot plots showing AUCs (95% CI) of proteins with reported relevance to pancreatic cancer for distinguishing cases from respective controls. (D) Dot plot AUCs (95% CI) of neuronal-associated proteins for distinguishing cases from respective controls. Abbreviations: AUC, area under the receiver operating characteristic curve; CHG, chromogranin; CI, confidence interval; dpNET, duodenopancreatic neuroendocrine tumor.