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      Ex Vivo 1H NMR study of pituitary adenomas to differentiate various immunohistochemical subtypes

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      Author(s): 1 , 1 , 2 , , 1 , 2 ,
      Publication date (Electronic):
      Journal: Scientific Reports
      Publisher: Nature Publishing Group UK

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          Abstract

          Pituitary adenomas (PAs) are benign growths arising from epithelial cells in the adenohypophysis of the pituitary gland. To date, there has been no detailed metabolic characterization of PAs of various subtypes. In this study, we report nuclear magnetic resonance (NMR) based metabolomic analysis of surgically resected tumors from forty five pituitary tumor patients [gonadotropic (LH/FSH-secreting) = 17; prolactinomas (PRL-secreting) = 11, Cushing’s disease (ACTH-secreting) = 4, non-functional = 5, and mixed = 8] who underwent transsphenoidal selective adenomectomy. Compared to LH/FSH-secreting tumors, PRL-secreting tumors showed statistically significant decrease in the levels of N-acetylaspartate (NAA), myo-inositol (mI), scyllo-inositol (sI), glycine, taurine, phosphoethanolamine (PE) and increase in the levels of glutamine. When compared with LH/FSH-secreting tumors, ACTH-secreting tumors showed statistically significant decrease in the levels of sI, glycine, PE and increase in the levels of aspartate. Although lipid extracts of PAs showed the presence of many common lipid molecules, only glycerophosphoethanolamine (GPE) showed statistically significant decrease in PRL, ACTH and non-functional subtypes when compared to LH/FSH-secreting tumors. Changes observed in these metabolite concentrations among various subtypes of PAs reflect metabolic heterogeneity in these tumors and may pave the way towards the development of metabolic markers to distinguish various immunohistochemical subtypes of PAs.

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          Lipid and metabolite profiles of human brain tumors by desorption electrospray ionization-MS.

          Alan Jarmusch, Valentina Pirro, Zane Baird … (2016)
          Examination of tissue sections using desorption electrospray ionization (DESI)-MS revealed phospholipid-derived signals that differ between gray matter, white matter, gliomas, meningiomas, and pituitary tumors, allowing their ready discrimination by multivariate statistics. A set of lower mass signals, some corresponding to oncometabolites, including 2-hydroxyglutaric acid and N-acetyl-aspartic acid, was also observed in the DESI mass spectra, and these data further assisted in discrimination between brain parenchyma and gliomas. The combined information from the lipid and metabolite MS profiles recorded by DESI-MS and explored using multivariate statistics allowed successful differentiation of gray matter (n = 223), white matter (n = 66), gliomas (n = 158), meningiomas (n = 111), and pituitary tumors (n = 154) from 58 patients. A linear discriminant model used to distinguish brain parenchyma and gliomas yielded an overall sensitivity of 97.4% and a specificity of 98.5%. Furthermore, a discriminant model was created for tumor types (i.e., glioma, meningioma, and pituitary), which were discriminated with an overall sensitivity of 99.4% and a specificity of 99.7%. Unsupervised multivariate statistics were used to explore the chemical differences between anatomical regions of brain parenchyma and secondary infiltration. Infiltration of gliomas into normal tissue can be detected by DESI-MS. One hurdle to implementation of DESI-MS intraoperatively is the need for tissue freezing and sectioning, which we address by analyzing smeared biopsy tissue. Tissue smears are shown to give the same chemical information as tissue sections, eliminating the need for sectioning before MS analysis. These results lay the foundation for implementation of intraoperative DESI-MS evaluation of tissue smears for rapid diagnosis.
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            Plasmalogen homeostasis - regulation of plasmalogen biosynthesis and its physiological consequence in mammals

            Masanori Honsho, Yukio Fujiki (2017)
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              Simultaneous extraction of cellular lipids and water-soluble metabolites: evaluation by NMR spectroscopy.

              R. D. Tyagi, A Azrad, Luiza H. Degani-Costa … (1996)
              A method for simultaneous extraction of lipids and water-soluble metabolites from a single cell sample was developed and optimized for NMR spectroscopy. Intermediary metabolites in cultured M2R mouse melanoma cells and changes therein in response to challenge with melanotropin were studied by 31P and 13C NMR. Cells were extracted with methanol, chloroform, and water (1:1:1, v/v/v). The contents of the chloroform and methanol-water phases were separated and quantitatively recovered. The contents of the upper and lower phases compared well with the homologous fractions obtained by perchloric acid and Folch's lipid extraction methods. The pH of the extracts remained within the physiologic range, eliminating potential deleterious effect on cellular metabolites. The water phase contained minimal amounts of salts, making these extracts amenable to subsequent analytical procedures. Obtaining lipid- and water-soluble metabolites from the same sample enables characterization of metabolic pathways that bridge the two cellular components in a quantitative manner.
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                Author and article information

                Contributors
                David S. Baskin: dbaskin@houstonmethodist.org
                Kumar Pichumani: kpichumani@houstonmethodist.org
                Journal
                Journal ID (nlm-ta): Sci Rep
                Journal ID (iso-abbrev): Sci Rep
                Title: Scientific Reports
                Publisher: Nature Publishing Group UK (London )
                ISSN (Electronic): 2045-2322
                Publication date (Electronic): 28 February 2019
                Publication date PMC-release: 28 February 2019
                Publication date Collection: 2019
                Volume: 9
                Electronic Location Identifier: 3007
                Affiliations
                [1 ]ISNI 0000 0004 0445 0041, GRID grid.63368.38, Kenneth R. Peak Brain and Pituitary Tumor Treatment Center, Department of Neurosurgery, Houston Methodist Neurological Institute, Houston Methodist Hospital and Research Institute, ; Houston, TX USA
                [2 ]ISNI 000000041936877X, GRID grid.5386.8, Weill Cornell Medical College, ; New York, NY USA
                Article
                Publisher ID: 38542
                DOI: 10.1038/s41598-019-38542-6
                PMC ID: 6395808
                PubMed ID: 30816132
                SO-VID: 87443aac-d2e8-45f6-9253-8b2d38d3d8eb
                Copyright © © The Author(s) 2019
                License:

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                Date received : 11 April 2018
                Date accepted : 28 December 2018
                Funding
                Funded by: The Veralan Foundation The Marilee A. and Gary M. Schwarz Foundation The John S. Dunn Foundation
                Funded by: The Donna and Kenneth Peak Foundation The Houston Methodist Foundation The Taub Foundation The Pauline Sterne Wolff Foundation The Veralan Foundation The Marilee A. and Gary M. Schwarz Foundation The John S. Dunn Foundation
                Categories
                Subject: Article
                Custom metadata
                issue-copyright-statement © The Author(s) 2019

                ScienceOpen disciplines: Uncategorized
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