Potential serum biomarkers for glioblastoma diagnostic assessed by proteomic approaches

Abstract

BackgroundThe rapid progress of proteomics over the past years has allowed the discovery of a large number of potential biomarker candidates to improve early tumor diagnosis and therapeutic response, thus being further integrated into clinical environment. High grade gliomas represent one of the most aggressive and treatment-resistant types of human brain cancer, with approximately 9–12 months median survival rate for patients with grade IV glioma (glioblastoma). Using state-of-the-art proteomics technologies, we have investigated the proteome profile for glioblastoma patients in order to identify a novel protein biomarker panel that could discriminate glioblastoma patients from controls and increase diagnostic accuracy.ResultsIn this study, SELDI-ToF MS technology was used to screen potential protein patterns in glioblastoma patients serum; furthermore, LC-MS/MS technology was applied to identify the candidate biomarkers peaks. Through these proteomic approaches, three proteins S100A8, S100A9 and CXCL4 were selected as putative biomarkers and confirmed by ELISA. Next step was to validate the above mentioned molecules as biomarkers through identification of protein expression by Western blot in tumoral versus peritumoral tissue.ConclusionsProteomic technologies have been used to investigate the protein profile of glioblastoma patients and established several potential diagnostic biomarkers. While it is unlikely for a single biomarker to be highly effective for glioblastoma diagnostic, our data proposed an alternative and efficient approach by using a novel combination of multiple biomarkers.

Definition of a serum marker panel for glioblastoma discrimination and identification of Interleukin 1β in the microglial secretome as a novel mediator of endothelial cell survival induced by C-reactive protein

“…Further, YKL40 and MMP9 levels in sera from post-operative period were found reduced in patients with no radiographic evidence of disease suggesting their utility in treatment monitoring [41]. Recently, using Surface-enhanced laser desorption/ionization timeof-flight mass spectrometry (SELDI-TOF) proteomic approach three molecules namely-S100A8, S100A9 and CXCL4 were identified as putative biomarkers for GBM [43]. Serum level of B-chain of α 2 -Heremans-Schmid glycoprotein (AHSG) was found to be decreased in majority of the GBM samples when compared to normal samples and had a good prognostic value [44].…”

Prostate cancer proteomics: Current trends and future perspectives for biomarker discovery

“…2D/DIGE represents a “common” approach in the discovery of PCa biomarkers, using as starting material serum, plasma, tissue samples from patients, as well as various cell cultures featuring the cancers under observation [27]. Using the 2D-DIGE approach, 118 proteins with significantly altered expression were identified by Ummanni et al in prostatic tissue tumor vs .…”

Cerebrospinal fluid and serum IL-8, CCL2, and ICAM-1 concentrations in astrocytic brain tumor patients

“…Simultaneous evaluation of multiple proteins in serum and cerebrospinal fluid allows for the identification of novel circulating biomarker panels helpful in disease diagnosis and treatment [4]. Therefore, in the last few years, proteomic approaches have been used to indicate potential cytokines, chemokines, and angiogenic factors for diagnosis and/or progression of primary brain tumors [1,5,6]. Using throughput xMAP technology, Albulescu et al identified serum profiles of cytokines and angiogenic factors (IL-6, IL-1β, IL-2, IL-10, TNF-α, VEGF, FGF-2, and GM-CSF) altered in glioblastoma patients [1].…”

“…The authors highlighted that the evaluation of biomarker panels is more appropriate than single molecule analysis [1]. Studies by Popescu et al also indicated the role of simultaneous identification of proteomic signature in the diagnosis and treatment of brain tumors, as they, by means of SELDI-ToF MS technology, indicated serum S100A8, S100A9, and CXCL4 proteins as a potential candidate for glioblastoma biomarkers [5]. A bio-plex system multimarker screening by Nijaguna et al, of circulating serum biomarkers in glioma patients, indicated 18 cytokines (interleukins: -2, -3, -4, -6, -7, -10, -12, -17, -15, MIP1 α, LIF, TNF-α, FGF basic, GM-CSF, IFN-γ, IL1Rα, SCGFβ, and βNGF) discriminating glioma patients from healthy individuals [6].…”