title: Identification of candidate serum proteins for classifying well-differentiated small intestinal neuroendocrine tumors.
abstract: BACKGROUND
  Patients with well-differentiated small intestine neuroendocrine tumors (WD-SI-NETs) are most often diagnosed at a metastatic stage of disease, which reduces possibilities for a curative treatment. Thus new approaches for earlier detection and improved monitoring of the disease are required.
  
  
  METHODS
  Suspension bead arrays targeting 124 unique proteins with antibodies from the Human Protein Atlas were used to profile biotinylated serum samples. Discoveries from a cohort of 77 individuals were followed up in a cohort of 132 individuals both including healthy controls as well as patients with untreated primary WD-SI-NETs, lymph node metastases and liver metastases.
  
  
  RESULTS
  A set of 20 antibodies suggested promising proteins for further verification based on technically verified statistical significance. Proceeding, we assessed the classification performance in an independent cohort of patient serum, achieving, classification accuracy of up to 85% with different subsets of antibodies in respective pairwise group comparisons. The protein profiles of nine targets, namely IGFBP2, IGF1, SHKBP1, ETS1, IL1α, STX2, MAML3, EGR3 and XIAP were verified as significant contributors to tumor classification.
  
  
  CONCLUSIONS
  We propose new potential protein biomarker candidates for classifying WD-SI-NETs at different stage of disease. Further evaluation of these proteins in larger sample sets and with alternative approaches is needed in order to further improve our understanding of their functional relation to WD-SI-NETs and their eventual use in diagnostics.
authors.affiliation: Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden ; Science for Life Laboratory, Uppsala, Sweden.
authors.forename: Spyros
authors.initials: S
authors.lastname: Darmanis
authors.forename: Tao
authors.initials: T
authors.lastname: Cui
authors.forename: Kimi
authors.initials: K
authors.lastname: Drobin
authors.forename: Su-Chen
authors.initials: SC
authors.lastname: Li
authors.forename: Kjell
authors.initials: K
authors.lastname: Öberg
authors.forename: Peter
authors.initials: P
authors.lastname: Nilsson
authors.forename: Jochen M
authors.initials: JM
authors.lastname: Schwenk
authors.forename: Valeria
authors.initials: V
authors.lastname: Giandomenico
mesh_terms: D001798:Blood Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D002454:Cell Differentiation; D006801:Humans; D007414:Intestinal Neoplasms / Q000097:blood / Q000145:classification* / Q000473:pathology; D007421:Intestine, Small / Q000473:pathology*; D018358:Neuroendocrine Tumors / Q000097:blood / Q000145:classification* / Q000473:pathology
chemical_list: D001798:Blood Proteins