Blood-based Proteomic Signatures Associated With MENI-related Duodenopancreatic Neuroendocrine Tumor Progression

Purpose: Patients with multiple endocrine neoplasia type 1 (MEND 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 patient...

Full description

Saved in:
Bibliographic Details
Published in:The journal of clinical endocrinology and metabolism 2023-12, Vol.108 (12), p.3260
Main Authors: Fahrmann, Johannes F, Wasylishen, Amanda R, Pieterman, Carolina R.C, Irajizad, Ehsan, Vykoukal, Jody, Wu, Ranran, Dennison, Jennifer B, Peterson, Christine B, Zhao, Hua, Do, Kim-Anh, Halperin, Daniel M, Agarwal, Sunita K, Blau, Jenny E, Jha, Smita, Del Rivero, Jaydira, Nilubol, Naris, Walter, Mary F, Welch, James M, Weinstein, Lee S, Vriens, Menno R, van Leeuwaarde, Rachel S, van Treijen, Mark J.C, Valk, Gerlof D, Perrier, Nancy D, Hanash, Samir M, Katayama, Hiroyuki
Format: Article
Language:English
Subjects:
Development and progression
Ethylenediaminetetraacetic acid
Medical centers
Pancreatic cancer
Proteins
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Purpose: Patients with multiple endocrine neoplasia type 1 (MEND 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 (Men[1.sup.fl/fl]Pdx-Cr[e.sup.Tg]) and control mice (Me[n.sup.fl/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 (Men[1.sup.fl/fl]Pdx-Cr[e.sup.Tg]) mice. Cross-species intersection revealed 19 proteins positively associated with disease progression in both human patients and in (Men[1.sup.fl/fl]Pdx-Cr[e.sup.Tg]) mice. Conclusions: Our integrated analyses identified novel circulating protein markers associated with disease progression in MEN1-related dpNET. Key Words: biomarkers, prognosis, multiple endocrine neoplasia type 1, duodenopancreatic neuroendocrine tumors
ISSN:0021-972X
DOI:10.1210/clinem/dgad315