title: Whole Reproductive System Non-Negative Matrix Factorization Mass Spectrometry Imaging of an Early-Stage Ovarian Cancer Mouse Model.
abstract: High-grade serous carcinoma (HGSC) is the most common and deadliest form of ovarian cancer. Yet it is largely asymptomatic in its initial stages. Studying the origin and early progression of this disease is thus critical in identifying markers for early detection and screening purposes. Tissue-based mass spectrometry imaging (MSI) can be employed as an unbiased way of examining localized metabolic changes between healthy and cancerous tissue directly, at the onset of disease. In this study, we describe MSI results from Dicer-Pten double-knockout (DKO) mice, a mouse model faithfully reproducing the clinical nature of human HGSC. By using non-negative matrix factorization (NMF) for the unsupervised analysis of desorption electrospray ionization (DESI) datasets, tissue regions are segregated based on spectral components in an unbiased manner, with alterations related to HGSC highlighted. Results obtained by combining NMF with DESI-MSI revealed several metabolic species elevated in the tumor tissue and/or surrounding blood-filled cyst including ceramides, sphingomyelins, bilirubin, cholesterol sulfate, and various lysophospholipids. Multiple metabolites identified within the imaging study were also detected at altered levels within serum in a previous metabolomic study of the same mouse model. As an example workflow, features identified in this study were used to build an oPLS-DA model capable of discriminating between DKO mice with early-stage tumors and controls with up to 88% accuracy.
authors.affiliation: School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, 30332, United States of America.
authors.forename: Martin R L
authors.identifier: 0000-0002-9360-1969
authors.initials: MR
authors.lastname: Paine
authors.affiliation: Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, 77030, United States of America.
authors.forename: Jaeyeon
authors.initials: J
authors.lastname: Kim
authors.affiliation: School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, 30332, United States of America.
authors.forename: Rachel V
authors.initials: RV
authors.lastname: Bennett
authors.affiliation: Department of Computer Science, Appalachian State University, Boone, NC, 28608, United States of America.
authors.forename: R Mitchell
authors.initials: RM
authors.lastname: Parry
authors.affiliation: School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, 30332, United States of America.|School of Biology, Georgia Institute of Technology, Atlanta, GA, 30332, United States of America.|Integrated Cancer Research Center, Georgia Institute of Technology, Atlanta, GA, 30332, United States of America.
authors.forename: David A
authors.initials: DA
authors.lastname: Gaul
authors.affiliation: Walter H. Coulter Department of Biomedical Engineering Georgia Institute of Technology, Atlanta, GA, 30332, United States of America.
authors.forename: May D
authors.initials: MD
authors.lastname: Wang
authors.affiliation: Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, 77030, United States of America.|Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, United States of America.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, United States of America.|Department of Pharmacology, Baylor College of Medicine, Houston, TX, 77030, United States of America.|Center for Drug Discovery, Baylor College of Medicine, Houston, TX, 77030, United States of America.|Center for Reproductive Medicine, Baylor College of Medicine, Houston, TX, 77030, United States of America.
authors.forename: Martin M
authors.initials: MM
authors.lastname: Matzuk
authors.affiliation: School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, 30332, United States of America.|Integrated Cancer Research Center, Georgia Institute of Technology, Atlanta, GA, 30332, United States of America.|Institute of Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, 30332, United States of America.
authors.forename: Facundo M
authors.initials: FM
authors.lastname: Fernández
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D013058:Mass Spectrometry / Q000379:methods*; D051379:Mice; D018345:Mice, Knockout; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging*; D051059:PTEN Phosphohydrolase / Q000235:genetics; D012098:Reproduction; D043244:Ribonuclease III / Q000235:genetics
chemical_list: D043244:Ribonuclease III; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse