title: Identification of serum proteome signatures of locally advanced and metastatic gastric cancer: a pilot study.
abstract: BACKGROUND
  The gastric cancer is one of the most common and mortal cancer worldwide. The initial asymptomatic development and further nonspecific symptoms result in diagnosis at the advanced stage with poor prognosis. Yet, no clinically useful biomarkers are available for this malignancy, and invasive gastrointestinal endoscopy remains the only reliable option at the moment. Hence, there is a need for discovery of clinically useful noninvasive diagnostic and/or prognostic tool as an alternative (or complement) for current diagnostic tools. Here we aimed to search for serum proteins characteristic for local and invasive gastric cancer.
  
  
  METHODS
  Pre-treatment blood samples were collected from patients with diagnosed gastric adenocarcinoma at the different stage of disease: 35 patients with locally advanced cancer and 18 patients with metastatic cancer; 50 healthy donors were also included as a control group. The low-molecular-weight fraction of serum proteome (i.e., endogenous peptidome) was profiled by the MALDI-ToF mass spectrometry, and the whole proteome components were identified and quantified by the LC-MS/MS shotgun approach.
  
  
  RESULTS
  Multicomponent peptidome signatures were revealed that allowed good discrimination between healthy controls and cancer patients, as well as between patients with locally advanced and metastatic cancer. Moreover, a LC-MS/MS approach revealed 49 serum proteins with different abundances between healthy donors and cancer patients (predominantly proteins associated with inflammation and acute phase response). Furthermore, 19 serum proteins with different abundances between patients with locally advanced and metastatic cancer were identified (including proteins associated with cytokine/chemokine response and metabolism of nucleic acids). However, neither peptidome profiling nor shotgun proteomics approach allowed detecting serum components discriminating between two subgroups of patients with local disease who either developed or did not develop metastases during follow-up.
  
  
  CONCLUSIONS
  The molecular differences between locally advanced and metastatic gastric cancer, as well as more obvious differences between healthy individuals and cancer patients, have marked reflection at the level of serum proteome. However, we have no evidence that features of pre-treatment serum proteome could predict a risk of cancer dissemination in patients treated due to local disease. Nevertheless, presented data confirmed potential applicability of a serum proteome signature-based biomarker in diagnostics of gastric cancer.
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland. Agata.Abramowicz@io.gliwice.pl.
authors.forename: Agata
authors.initials: A
authors.lastname: Abramowicz
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland. Anna.Wojakowska@io.gliwice.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Wojakowska
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland. Agnieszka.GdowiczKlosok@io.gliwice.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gdowicz-Klosok
authors.affiliation: Silesian University of Technology, Gliwice, Poland. Joanna.Polanska@polsl.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Polanska
authors.affiliation: Institute of Bioorganic Chemistry, Polish Academy of Science, Poznan, Poland. prod@ibch.poznan.pl.
authors.forename: Pawel
authors.initials: P
authors.lastname: Rodziewicz
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland. PolanowskiPawel@gmail.com.
authors.forename: Pawel
authors.initials: P
authors.lastname: Polanowski
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland. Aga.Kaletka@wp.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Namysl-Kaletka
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland. Monika.Pietrowska@io.gliwice.pl.
authors.forename: Monika
authors.initials: M
authors.lastname: Pietrowska
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland. jerzywydmanski@gmail.com.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Wydmanski
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland. piotr.widlak@io.gliwice.pl.
authors.forename: Piotr
authors.initials: P
authors.lastname: Widlak
mesh_terms: D000230:Adenocarcinoma / Q000097:blood*; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D001798:Blood Proteins / Q000737:chemistry*; D002853:Chromatography, Liquid; D019295:Computational Biology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009362:Neoplasm Metastasis; D010455:Peptides / Q000737:chemistry; D010865:Pilot Projects; D011379:Prognosis; D020543:Proteome; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013274:Stomach Neoplasms / Q000097:blood*; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D010455:Peptides; D020543:Proteome