Blood-based Proteomic Signatures Associated With MEN1-related Duodenopancreatic Neuroendocrine Tumor Progression.

Autor:	Fahrmann JF; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Wasylishen AR; Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Department of Cancer Biology, University of Cincinnati, Cincinnati, OH 45267, USA., Pieterman CRC; Department of Surgical Oncology, Section of Surgical Endocrinology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht 3508 GA, the Netherlands., Irajizad E; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Vykoukal J; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Wu R; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Dennison JB; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Peterson CB; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Zhao H; Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Department of Family Medicine and Population Health, Virginia Commonwealth University, Richmond, VA 23284, USA., Do KA; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Halperin DM; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Agarwal SK; Metabolic Diseases Branch, The National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Blau JE; Metabolic Diseases Branch, The National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Jha S; Metabolic Diseases Branch, The National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Rivero JD; Developmental Therapeutics Branch, The National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Nilubol N; Surgical Oncology Program, The National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Walter MF; Core for Clinical Laboratory Services, The National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Welch JM; Metabolic Diseases Branch, The National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Weinstein LS; Metabolic Diseases Branch, The National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Vriens MR; Department of Surgical Oncology and Endocrine Surgery, University Medical Center Utrecht, Utrecht 3584 CX, the Netherlands.; Center for Neuroendocrine Tumors, ENETS Center of Excellence, Netherlands Cancer Institute Amsterdam, University Medical Center Utrecht, Utrect 1066 CX, the Netherlands., van Leeuwaarde RS; Center for Neuroendocrine Tumors, ENETS Center of Excellence, Netherlands Cancer Institute Amsterdam, University Medical Center Utrecht, Utrect 1066 CX, the Netherlands.; Department of Cancer Biology, University of Cincinnati, Cincinnati, OH 45267, USA., van Treijen MJC; Center for Neuroendocrine Tumors, ENETS Center of Excellence, Netherlands Cancer Institute Amsterdam, University Medical Center Utrecht, Utrect 1066 CX, the Netherlands.; Department of Cancer Biology, University of Cincinnati, Cincinnati, OH 45267, USA., Valk GD; Center for Neuroendocrine Tumors, ENETS Center of Excellence, Netherlands Cancer Institute Amsterdam, University Medical Center Utrecht, Utrect 1066 CX, the Netherlands.; Department of Cancer Biology, University of Cincinnati, Cincinnati, OH 45267, USA., Perrier ND; Department of Surgical Oncology, Section of Surgical Endocrinology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Hanash SM; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Katayama H; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jazyk:	angličtina
Zdroj:	The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2023 Nov 17; Vol. 108 (12), pp. 3260-3271.
DOI:	10.1210/clinem/dgad315
Abstrakt:	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. (© 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.)
Databáze:	MEDLINE
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