TY - JOUR
T1 - Blood-based proteomic signatures associated with MEN1-related Duodenopancreatic Neuroendocrine Tumor Progression
AU - Fahrmann, Johannes F
AU - Wasylishen, Amanda R
AU - Pieterman, Carolina R C
AU - Irajizad, Ehsan
AU - Vykoukal, Jody
AU - Wu, Ranran
AU - Dennison, Jennifer B
AU - Peterson, Christine B
AU - Zhao, Hua
AU - Do, Kim-Anh
AU - Halperin, Daniel M
AU - Agarwal, Sunita K
AU - Blau, Jenny E
AU - Jha, Smita
AU - Rivero, Jaydira Del
AU - Nilubol, Naris
AU - Walter, Mary F
AU - Welch, James M
AU - Weinstein, Lee S
AU - Vriens, Menno R
AU - van Leeuwaarde, Rachel S
AU - van Treijen, Mark J C
AU - Valk, Gerlof D
AU - Perrier, Nancy D
AU - Hanash, Samir M
AU - Katayama, Hiroyuki
N1 - Publisher Copyright:
© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.
PY - 2023/11/17
Y1 - 2023/11/17
N2 - PURPOSE: Patients with Multiple Endocrine Neoplasia Type 1 (MEN1) are predisposed to develop duodenopancreatic neuroendocrine tumors (dpNETs) and metastatic dpNET is the primary cause of disease-related mortality. Presently, there is a paucity of prognostic factors that can reliably identify patients with MEN1-related dpNETS who are at high risk of distant metastasis. In the current study, we aimed to establish novel circulating molecular protein signatures associated with disease progression.EXPERIMENTAL DESIGN: Mass spectrometry-based proteomic profiling was conducted on plasmas procured through an international collaboration between MD Anderson Cancer Center, the National Institutes of Health, and the University Medical Center Utrecht from a cohort of 56 patients with MEN1 (14 with distant metastasis dpNETs (cases) and 42 with either indolent dpNETs or no dpNETs (controls)). Findings were compared to proteomic profiles generated from serially collected plasmas from a mouse model of Men1-pancreatic neuroendocrine tumors (Men1fl/flPdx1-CreTg) and control mice (Men1fl/fl).RESULTS: A total of 187 proteins were found to be elevated in MEN1 patients with distant metastasis compared to controls, including 9 proteins previously associated with pancreatic cancer and other neuronal proteins. Analyses of mouse plasmas revealed 196 proteins enriched for transcriptional targets of oncogenic MYCN, YAP1, POU5F1, and SMAD that were associated with disease progression in Men1fl/flPdx1-CreTg mice. Cross-species intersection revealed 19 proteins positively associated with disease progression in both human patients and in Men1fl/flPdx1-CreTg mice.CONCLUSIONS: Our integrated analyses identified novel circulating protein markers associated with disease progression in MEN1-related dpNET.
AB - PURPOSE: Patients with Multiple Endocrine Neoplasia Type 1 (MEN1) are predisposed to develop duodenopancreatic neuroendocrine tumors (dpNETs) and metastatic dpNET is the primary cause of disease-related mortality. Presently, there is a paucity of prognostic factors that can reliably identify patients with MEN1-related dpNETS who are at high risk of distant metastasis. In the current study, we aimed to establish novel circulating molecular protein signatures associated with disease progression.EXPERIMENTAL DESIGN: Mass spectrometry-based proteomic profiling was conducted on plasmas procured through an international collaboration between MD Anderson Cancer Center, the National Institutes of Health, and the University Medical Center Utrecht from a cohort of 56 patients with MEN1 (14 with distant metastasis dpNETs (cases) and 42 with either indolent dpNETs or no dpNETs (controls)). Findings were compared to proteomic profiles generated from serially collected plasmas from a mouse model of Men1-pancreatic neuroendocrine tumors (Men1fl/flPdx1-CreTg) and control mice (Men1fl/fl).RESULTS: A total of 187 proteins were found to be elevated in MEN1 patients with distant metastasis compared to controls, including 9 proteins previously associated with pancreatic cancer and other neuronal proteins. Analyses of mouse plasmas revealed 196 proteins enriched for transcriptional targets of oncogenic MYCN, YAP1, POU5F1, and SMAD that were associated with disease progression in Men1fl/flPdx1-CreTg mice. Cross-species intersection revealed 19 proteins positively associated with disease progression in both human patients and in Men1fl/flPdx1-CreTg mice.CONCLUSIONS: Our integrated analyses identified novel circulating protein markers associated with disease progression in MEN1-related dpNET.
KW - biomarkers
KW - duodenopancreatic neuroendocrine tumors
KW - multiple endocrine neoplasia type 1
KW - prognosis
UR - http://www.scopus.com/inward/record.url?scp=85175371689&partnerID=8YFLogxK
U2 - 10.1210/clinem/dgad315
DO - 10.1210/clinem/dgad315
M3 - Article
C2 - 37307230
SN - 0021-972X
VL - 108
SP - 3260
EP - 3271
JO - The Journal of clinical endocrinology and metabolism
JF - The Journal of clinical endocrinology and metabolism
IS - 12
ER -