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

Abstract

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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0668-9) contains supplementary material, which is available to authorized users.

Coagulation and fibrinolysis in gastric cancer

“…The GC patients globally showed higher levels of FpA compared with healthy controls, so FpA was proposed as a potential marker for GC detection (Table ). Serum peptidome analyses by either matrix‐assisted laser‐desorption ionization or surface‐enhanced laser‐desorption ionization time‐of‐flight mass spectrometry revealed FpA peptide as a m/z peak at around 1469 Da particularly upregulated in metastatic GC or in GC with lymph node metastasis, as well as in patients at high risk for GC . Previous laboratory assays showed that FpA levels increased with the extent of primary tumor in postoperative patients with malignant disease since its early stages …”

“…Serum peptidome analyses by either matrix-assisted laser-desorption ionization or surface-enhanced laser-desorption ionization time-of-flight mass spectrometry revealed FpA peptide as a m/z peak at around 1469 Da particularly upregulated in metastatic GC or in GC with lymph node metastasis, as well as in patients at high risk for GC. [120][121][122][123] Previous laboratory assays showed that FpA levels increased with the extent of primary tumor in postoperative patients with malignant disease since its early stages. [124][125][126][127] Fibrinolysis: DD as an indicator of thrombosis, cancer progression, and response to therapy As a compensation mechanism for fibrin clot formation, fibrinolysis is activated, which consists of fibrin degradation by the sequential action of three enzymes: thrombin, factor XIIIa, and plasmin.…”

Identification of Serum Peptidome Signatures of Non-Small Cell Lung Cancer

“…The use of MALDI-TOF-MS profiling enables to obtain a whole pattern of low-molecular weight proteins occurring in human serum and was indicated as a promising strategy in several cancer research. This technology was found to be effective in discrimination of healthy individuals from patients with various tumors such as biliary tract cancer [ 32 ], gastric cancer [ 33 ], prostate cancer [ 34 ], ovarian cancer [ 16 ] and head and neck cancer [ 35 ]. Moreover, serum peptidome features were suggested to be useful in monitoring the toxicity of applied therapy in women with breast cancer [ 36 ].…”

Systems Biology of Gastric Cancer: Perspectives on the Omics-Based Diagnosis and Treatment

“…Proteomics complements the genomic and transcriptomics approaches, providing additional information about the protein expression and post-translational modifications. Most of proteomics studies in this field so far focused on the discovery of gastric cancer associated biomarkers from plasma samples (Uen et al, 2013;Abramowicz et al, 2015;Gao et al, 2015;Yoo et al, 2017). An early study (Uen et al, 2013) investigated the glycoprotein profiles of serum samples from gastric cancer patients and healthy subjects.…”