Identification of serum proteome signatures of locally advanced and metastatic gastric cancer: a pilot study

Journal of Translational Medicine

Research

Pawel Rodziewicz¹  Agnieszka Gdowicz-Klosok²  Anna Wojakowska²  Piotr Widlak²  Monika Pietrowska²  Pawel Polanowski²  Jerzy Wydmanski²  Agata Abramowicz²  Agnieszka Namysl-Kaletka²  Joanna Polanska³ 

[1] Institute of Bioorganic Chemistry, Polish Academy of Science, Poznan, Poland;Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland;Silesian University of Technology, Gliwice, Poland;

关键词: Stomach cancer;    Early diagnosis;    Neoplasms;    Proteomics;    Biological markers;   

DOI  :  10.1186/s12967-015-0668-9

 received in 2015-06-13, accepted in 2015-09-10,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsPre-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.ResultsMulticomponent 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.ConclusionsThe 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.

【 授权许可】

CC BY   
© Abramowicz et al. 2015