title: High-grade sarcoma diagnosis and prognosis: Biomarker discovery by mass spectrometry imaging.
abstract: The combination of high heterogeneity, both intratumoral and intertumoral, with their rarity has made diagnosis, prognosis of high-grade sarcomas difficult. There is an urgent need for more objective molecular biomarkers, to differentiate between the many different subtypes, and to also provide new treatment targets. Mass spectrometry imaging (MSI) has amply demonstrated its ability to identify potential new markers for patient diagnosis, survival, metastasis and response to therapy in cancer research. In this study, we investigated the ability of MALDI-MSI of proteins to distinguish between high-grade osteosarcoma (OS), leiomyosarcoma (LMS), myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) (Ntotal = 53). We also investigated if there are individual proteins or protein signatures that are statistically associated with patient survival. Twenty diagnostic protein signals were found characteristic for specific tumors (p ≤ 0.05), amongst them acyl-CoA-binding protein (m/z 11 162), macrophage migration inhibitory factor (m/z 12 350), thioredoxin (m/z 11 608) and galectin-1 (m/z 14 633) were assigned. Another nine protein signals were found to be associated with overall survival (p ≤ 0.05), including proteasome activator complex subunit 1 (m/z 9753), indicative for non-OS patients with poor survival; and two histone H4 variants (m/z 11 314 and 11 355), indicative of poor survival for LMS patients.
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Sha
authors.initials: S
authors.lastname: Lou
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.|Maastricht MultiModal Molecular Imaging Institute, Maastricht University, Maastricht, The Netherlands.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Balluff
authors.affiliation: Department of Pathology, Leiden University, Medical Center, Leiden, The Netherlands.
authors.forename: Marieke A
authors.initials: MA
authors.lastname: de Graaff
authors.affiliation: Department of Pathology, Leiden University, Medical Center, Leiden, The Netherlands.
authors.forename: Arjen H G
authors.initials: AH
authors.lastname: Cleven
authors.affiliation: Department of Pathology, Leiden University, Medical Center, Leiden, The Netherlands.
authors.forename: Inge
authors.initials: I
authors.lastname: Briaire-de Bruijn
authors.affiliation: Department of Pathology, Leiden University, Medical Center, Leiden, The Netherlands.
authors.forename: Judith V M G
authors.initials: JV
authors.lastname: Bovée
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.|Department of Pathology, Leiden University, Medical Center, Leiden, The Netherlands.|Fondazione Pisana per la Scienza ONLUS, Pisa, Italy.
authors.forename: Liam A
authors.initials: LA
authors.lastname: McDonnell
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005354:Fibrosarcoma / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007890:Leiomyosarcoma / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D012516:Osteosarcoma / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D040901:Proteomics / Q000379:methods; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins
keywords: Biomarker discovery; Biomedicine; Intratumor heterogeneity; Mass spectrometry imaging; Soft tissue sarcoma