title: Novel molecular tumour classification using MALDI-mass spectrometry imaging of tissue micro-array.
abstract: The development of tissue micro-array (TMA) technologies provides insights into high-throughput analysis of proteomics patterns from a large number of archived tumour samples. In the work reported here, matrix-assisted laser desorption/ionisation-ion mobility separation-mass spectrometry (MALDI-IMS-MS) profiling and imaging methodology has been used to visualise the distribution of several peptides and identify them directly from TMA sections after on-tissue tryptic digestion. A novel approach that combines MALDI-IMS-MSI and principal component analysis-discriminant analysis (PCA-DA) is described, which has the aim of generating tumour classification models based on protein profile patterns. The molecular classification models obtained by PCA-DA have been validated by applying the same statistical analysis to other tissue cores and patient samples. The ability to correlate proteomic information obtained from samples with known and/or unknown clinical outcome by statistical analysis is of great importance, since it may lead to a better understanding of tumour progression and aggressiveness and hence improve diagnosis, prognosis as well as therapeutic treatments. The selectivity, robustness and current limitations of the methodology are discussed.
authors.affiliation: Biomedical Research Centre, Sheffield Hallam University, Howard Street, Sheffield, S1 1WB, UK.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Djidja
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Claude
authors.forename: Marten F
authors.initials: MF
authors.lastname: Snel
authors.forename: Simona
authors.initials: S
authors.lastname: Francese
authors.forename: Peter
authors.initials: P
authors.lastname: Scriven
authors.forename: Vikki
authors.initials: V
authors.lastname: Carolan
authors.forename: Malcolm R
authors.initials: MR
authors.lastname: Clench
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000595:Amino Acid Sequence; D006801:Humans; D008969:Molecular Sequence Data; D010190:Pancreatic Neoplasms / Q000473:pathology*; D011506:Proteins / Q000032:analysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D046888:Tissue Array Analysis / Q000379:methods*
chemical_list: D011506:Proteins