PMID- 37307230
OWN - NLM
STAT- MEDLINE
DCOM- 20231122
LR  - 20240426
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 108
IP  - 12
DP  - 2023 Nov 17
TI  - Blood-based Proteomic Signatures Associated With MEN1-related Duodenopancreatic 
      Neuroendocrine Tumor Progression.
PG  - 3260-3271
LID - 10.1210/clinem/dgad315 [doi]
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.
CI  - (c) The Author(s) 2023. Published by Oxford University Press on behalf of the 
      Endocrine Society. All rights reserved. For permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Fahrmann, Johannes F
AU  - Fahrmann JF
AD  - Department of Clinical Cancer Prevention, The University of Texas MD Anderson 
      Cancer Center, Houston, TX 77030, USA.
FAU - Wasylishen, Amanda R
AU  - Wasylishen AR
AD  - Department of Genetics, The University of Texas MD Anderson Cancer Center, 
      Houston, TX 77030, USA.
AD  - Department of Cancer Biology, University of Cincinnati, Cincinnati, OH 45267, 
      USA.
FAU - Pieterman, Carolina R C
AU  - Pieterman CRC
AD  - Department of Surgical Oncology, Section of Surgical Endocrinology, The 
      University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
AD  - Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht 3508 
      GA, the Netherlands.
FAU - Irajizad, Ehsan
AU  - Irajizad E
AD  - Department of Clinical Cancer Prevention, The University of Texas MD Anderson 
      Cancer Center, Houston, TX 77030, USA.
AD  - Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 
      Houston, TX 77030, USA.
FAU - Vykoukal, Jody
AU  - Vykoukal J
AD  - Department of Clinical Cancer Prevention, The University of Texas MD Anderson 
      Cancer Center, Houston, TX 77030, USA.
FAU - Wu, Ranran
AU  - Wu R
AD  - Department of Clinical Cancer Prevention, The University of Texas MD Anderson 
      Cancer Center, Houston, TX 77030, USA.
FAU - Dennison, Jennifer B
AU  - Dennison JB
AUID- ORCID: 0000-0003-3067-0972
AD  - Department of Clinical Cancer Prevention, The University of Texas MD Anderson 
      Cancer Center, Houston, TX 77030, USA.
FAU - Peterson, Christine B
AU  - Peterson CB
AD  - Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 
      Houston, TX 77030, USA.
FAU - Zhao, Hua
AU  - Zhao H
AD  - Department of Epidemiology, The University of Texas MD Anderson Cancer Center, 
      Houston, TX 77030, USA.
AD  - Department of Family Medicine and Population Health, Virginia Commonwealth 
      University, Richmond, VA 23284, USA.
FAU - Do, Kim-Anh
AU  - Do KA
AD  - Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 
      Houston, TX 77030, USA.
FAU - Halperin, Daniel M
AU  - Halperin DM
AD  - Department of Gastrointestinal Medical Oncology, The University of Texas MD 
      Anderson Cancer Center, Houston, TX 77030, USA.
FAU - Agarwal, Sunita K
AU  - Agarwal SK
AD  - Metabolic Diseases Branch, The National Institute of Diabetes and Digestive and 
      Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
FAU - Blau, Jenny E
AU  - Blau JE
AD  - Metabolic Diseases Branch, The National Institute of Diabetes and Digestive and 
      Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
FAU - Jha, Smita
AU  - Jha S
AUID- ORCID: 0000-0001-9201-3340
AD  - Metabolic Diseases Branch, The National Institute of Diabetes and Digestive and 
      Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
FAU - Rivero, Jaydira Del
AU  - Rivero JD
AD  - Developmental Therapeutics Branch, The National Cancer Institute, National 
      Institutes of Health, Bethesda, MD 20892, USA.
FAU - Nilubol, Naris
AU  - Nilubol N
AD  - Surgical Oncology Program, The National Cancer Institute, National Institutes of 
      Health, Bethesda, MD 20892, USA.
FAU - Walter, Mary F
AU  - Walter MF
AD  - Core for Clinical Laboratory Services, The National Institute of Diabetes and 
      Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, 
      USA.
FAU - Welch, James M
AU  - Welch JM
AD  - Metabolic Diseases Branch, The National Institute of Diabetes and Digestive and 
      Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
FAU - Weinstein, Lee S
AU  - Weinstein LS
AD  - Metabolic Diseases Branch, The National Institute of Diabetes and Digestive and 
      Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
FAU - Vriens, Menno R
AU  - Vriens MR
AD  - Department of Surgical Oncology and Endocrine Surgery, University Medical Center 
      Utrecht, Utrecht 3584 CX, the Netherlands.
AD  - Center for Neuroendocrine Tumors, ENETS Center of Excellence, Netherlands Cancer 
      Institute Amsterdam, University Medical Center Utrecht, Utrect 1066 CX, the 
      Netherlands.
FAU - van Leeuwaarde, Rachel S
AU  - van Leeuwaarde RS
AD  - Center for Neuroendocrine Tumors, ENETS Center of Excellence, Netherlands Cancer 
      Institute Amsterdam, University Medical Center Utrecht, Utrect 1066 CX, the 
      Netherlands.
AD  - Department of Cancer Biology, University of Cincinnati, Cincinnati, OH 45267, 
      USA.
FAU - van Treijen, Mark J C
AU  - van Treijen MJC
AD  - Center for Neuroendocrine Tumors, ENETS Center of Excellence, Netherlands Cancer 
      Institute Amsterdam, University Medical Center Utrecht, Utrect 1066 CX, the 
      Netherlands.
AD  - Department of Cancer Biology, University of Cincinnati, Cincinnati, OH 45267, 
      USA.
FAU - Valk, Gerlof D
AU  - Valk GD
AD  - Center for Neuroendocrine Tumors, ENETS Center of Excellence, Netherlands Cancer 
      Institute Amsterdam, University Medical Center Utrecht, Utrect 1066 CX, the 
      Netherlands.
AD  - Department of Cancer Biology, University of Cincinnati, Cincinnati, OH 45267, 
      USA.
FAU - Perrier, Nancy D
AU  - Perrier ND
AD  - Department of Surgical Oncology, Section of Surgical Endocrinology, The 
      University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
FAU - Hanash, Samir M
AU  - Hanash SM
AD  - Department of Clinical Cancer Prevention, The University of Texas MD Anderson 
      Cancer Center, Houston, TX 77030, USA.
FAU - Katayama, Hiroyuki
AU  - Katayama H
AUID- ORCID: 0000-0003-3117-1390
AD  - Department of Clinical Cancer Prevention, The University of Texas MD Anderson 
      Cancer Center, Houston, TX 77030, USA.
LA  - eng
GR  - P30 CA016672/CA/NCI NIH HHS/United States
GR  - P50 CA140388/CA/NCI NIH HHS/United States
GR  - UL1TR003167/GF/NIH HHS/United States
GR  - UL1 TR003167/TR/NCATS NIH HHS/United States
GR  - R01 GM122775/GM/NIGMS NIH HHS/United States
GR  - R21 CA252426/CA/NCI NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (MEN1 protein, human)
SB  - IM
CIN - J Clin Endocrinol Metab. 2023 Aug 30;:. PMID: 37646771
MH  - Animals
MH  - Humans
MH  - Mice
MH  - Disease Progression
MH  - *Multiple Endocrine Neoplasia Type 1/pathology
MH  - *Neuroendocrine Tumors/pathology
MH  - *Pancreatic Neoplasms/pathology
MH  - Proteomics
MH  - Proto-Oncogene Proteins
PMC - PMC11032251
OTO - NOTNLM
OT  - biomarkers
OT  - duodenopancreatic neuroendocrine tumors
OT  - multiple endocrine neoplasia type 1
OT  - prognosis
EDAT- 2023/06/12 19:12
MHDA- 2023/11/20 06:55
PMCR- 2024/06/12
CRDT- 2023/06/12 13:03
PHST- 2023/03/31 00:00 [received]
PHST- 2024/06/12 00:00 [pmc-release]
PHST- 2023/11/20 06:55 [medline]
PHST- 2023/06/12 19:12 [pubmed]
PHST- 2023/06/12 13:03 [entrez]
AID - 7194261 [pii]
AID - dgad315 [pii]
AID - 10.1210/clinem/dgad315 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2023 Nov 17;108(12):3260-3271. doi: 
      10.1210/clinem/dgad315.