PMID- 34318891
OWN - NLM
STAT- MEDLINE
DCOM- 20211229
LR  - 20220729
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 106
IP  - 12
DP  - 2021 Nov 19
TI  - A Blood-based Polyamine Signature Associated With MEN1 Duodenopancreatic 
      Neuroendocrine Tumor Progression.
PG  - e4969-e4980
LID - 10.1210/clinem/dgab554 [doi]
AB  - CONTEXT: 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. OBJECTIVE: We hypothesized that MEN1-dpNET-related disease 
      progression is associated with elevated levels of circulating polyamines. 
      METHODS: Through an international collaboration between The University of Texas 
      MD Anderson Cancer Center, the National Institutes of Health, and the University 
      Medical Center Utrecht, plasma polyamine levels were assessed using mass 
      spectrometry in 84 patients with MEN1 (20 with distant metastatic dpNETs 
      [patients] and 64 with either indolent dpNETs or no dpNETs [controls]). A mouse 
      model of MEN1-pNET, Men1fl/flPdx1-CreTg, was used to test time-dependent changes 
      in plasma polyamines associated with disease progression. RESULTS: 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 3 participating centers. The fixed 3MP 
      yielded an area under the curve of 0.84 (95% CI, 0.62-1.00) with 66.7% 
      sensitivity at 95% specificity for distinguishing patients from controls in an 
      independent test set from MDACC. In Men1fl/flPdx1-CreTg mice, the 3MP was 
      elevated early and remained high during disease progression. CONCLUSION: Our 
      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.
CI  - (c) The Author(s) 2021. 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
AUID- ORCID: 0000-0001-5088-0198
AD  - Department of Clinical Cancer Prevention, The University of Texas MD Anderson 
      Cancer Center, Houston, Texas, USA.
FAU - Wasylishen, Amanda R
AU  - Wasylishen AR
AD  - Department of Genetics, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas, 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, Texas, USA.
FAU - Irajizad, Ehsan
AU  - Irajizad E
AD  - Department of Clinical Cancer Prevention, The University of Texas MD Anderson 
      Cancer Center, Houston, Texas, USA.
AD  - Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas, USA.
FAU - Vykoukal, Jody
AU  - Vykoukal J
AD  - Department of Clinical Cancer Prevention, The University of Texas MD Anderson 
      Cancer Center, Houston, Texas, USA.
FAU - Murage, Eunice
AU  - Murage E
AD  - Department of Clinical Cancer Prevention, The University of Texas MD Anderson 
      Cancer Center, Houston, Texas, USA.
FAU - Wu, Ranran
AU  - Wu R
AD  - Department of Clinical Cancer Prevention, The University of Texas MD Anderson 
      Cancer Center, Houston, Texas, 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, Texas, USA.
FAU - Krishna, Hansini
AU  - Krishna H
AD  - Department of Clinical Cancer Prevention, The University of Texas MD Anderson 
      Cancer Center, Houston, Texas, USA.
FAU - Peterson, Christine B
AU  - Peterson CB
AD  - Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas, USA.
FAU - Lozano, Guillermina
AU  - Lozano G
AD  - Department of Genetics, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas, USA.
FAU - Zhao, Hua
AU  - Zhao H
AD  - Department of Epidemiology, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas, USA.
AD  - Department of Family Medicine and Population Health, Virginia Commonwealth 
      University, Richmond, Virgina, USA.
FAU - Do, Kim-Anh
AU  - Do KA
AD  - Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas, USA.
FAU - Halperin, Daniel M
AU  - Halperin DM
AD  - Department of Gastrointestinal Medical Oncology, The University of Texas MD 
      Anderson Cancer Center, Houston, Texas, USA.
FAU - Agarwal, Sunita K
AU  - Agarwal SK
AD  - Metabolic Diseases Branch, the National Cancer Institute, National Institutes of 
      Health, Bethesda, Maryland, USA.
FAU - Blau, Jenny E
AU  - Blau JE
AUID- ORCID: 0000-0002-6725-4262
AD  - Metabolic Diseases Branch, the National Cancer Institute, National Institutes of 
      Health, Bethesda, Maryland, USA.
FAU - Del Rivero, Jaydira
AU  - Del Rivero J
AUID- ORCID: 0000-0001-9710-4030
AD  - Developmental Therapeutics Branch, the National Cancer Institute, National 
      Institutes of Health, Bethesda, Maryland, USA.
FAU - Nilubol, Naris
AU  - Nilubol N
AUID- ORCID: 0000-0002-7348-7804
AD  - Surgical Oncology Program, the National Cancer Institute, National Institutes of 
      Health, Bethesda, Maryland, 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, Maryland, 
      USA.
FAU - Welch, James M
AU  - Welch JM
AD  - Metabolic Diseases Branch, the National Cancer Institute, National Institutes of 
      Health, Bethesda, Maryland, USA.
FAU - Weinstein, Lee S
AU  - Weinstein LS
AD  - Metabolic Diseases Branch, the National Cancer Institute, National Institutes of 
      Health, Bethesda, Maryland, USA.
FAU - Vriens, Menno R
AU  - Vriens MR
AD  - Department of Surgical Oncology and Endocrine Surgery, University Medical Center 
      Utrecht, 3584 CX Utrecht, the Netherlands.
AD  - Center for Neuroendocrine Tumors, ENETS Center of Excellence, Netherlands Cancer 
      Institute Amsterdam, University Medical Center Utrecht, 3584 CX Utrecht, 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, 3584 CX Utrecht, the 
      Netherlands.
AD  - Department of Endocrine Oncology, University Medical Center Utrecht, 3584 CX 
      Utrecht, the Netherlands.
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, 3584 CX Utrecht, the 
      Netherlands.
AD  - Department of Endocrine Oncology, University Medical Center Utrecht, 3584 CX 
      Utrecht, the Netherlands.
FAU - Valk, Gerlof D
AU  - Valk GD
AD  - Center for Neuroendocrine Tumors, ENETS Center of Excellence, Netherlands Cancer 
      Institute Amsterdam, University Medical Center Utrecht, 3584 CX Utrecht, the 
      Netherlands.
AD  - Department of Endocrine Oncology, University Medical Center Utrecht, 3584 CX 
      Utrecht, the Netherlands.
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, Texas, USA.
FAU - Hanash, Samir M
AU  - Hanash SM
AUID- ORCID: 0000-0002-4210-1593
AD  - Department of Clinical Cancer Prevention, The University of Texas MD Anderson 
      Cancer Center, Houston, Texas, USA.
LA  - eng
GR  - P30 CA016672/CA/NCI NIH HHS/United States
GR  - R21 CA252426-01/NH/NIH HHS/United States
GR  - P50 CA140388/CA/NCI NIH HHS/United States
GR  - UL1 TR003167/TR/NCATS NIH HHS/United States
GR  - NIH/NCI R21 CA252426-01/NH/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
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Polyamines)
SB  - IM
CIN - J Clin Endocrinol Metab. 2021 Sep 20;:. PMID: 34543418
MH  - Adult
MH  - Aged
MH  - Biomarkers, Tumor/*blood
MH  - Case-Control Studies
MH  - Disease Progression
MH  - Duodenal Neoplasms/blood/epidemiology/*pathology
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/blood/epidemiology/*pathology
MH  - Neuroendocrine Tumors/blood/epidemiology/*pathology
MH  - Pancreatic Neoplasms/blood/epidemiology/*pathology
MH  - Polyamines/*blood
MH  - Prognosis
MH  - Retrospective Studies
MH  - United States/epidemiology
MH  - Young Adult
PMC - PMC8864750
OTO - NOTNLM
OT  - biomarker
OT  - pancreatic neuroendocrine tumors
OT  - polyamines
EDAT- 2021/07/29 06:00
MHDA- 2021/12/30 06:00
PMCR- 2022/07/28
CRDT- 2021/07/28 08:52
PHST- 2021/04/14 00:00 [received]
PHST- 2021/07/29 06:00 [pubmed]
PHST- 2021/12/30 06:00 [medline]
PHST- 2021/07/28 08:52 [entrez]
PHST- 2022/07/28 00:00 [pmc-release]
AID - 6329395 [pii]
AID - dgab554 [pii]
AID - 10.1210/clinem/dgab554 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2021 Nov 19;106(12):e4969-e4980. doi: 
      10.1210/clinem/dgab554.