Serum biomarkers identification by iTRAQ and verification by MRM: S100A8/S100A9 levels predict tumor-stroma involvement and prognosis in Glioblastoma

Abstract

Despite advances in biology and treatment modalities, the prognosis of glioblastoma (GBM) remains poor. Serum reflects disease macroenvironment and thus provides a less invasive means to diagnose and monitor a diseased condition. By employing 4-plex iTRAQ methodology, we identified 40 proteins with differential abundance in GBM sera. The high abundance of serum S100A8/S100A9 was verified by multiple reaction monitoring (MRM). ELISA and MRM-based quantitation showed a significant positive correlation. Further, an integrated investigation using stromal, tumor purity and cell type scores demonstrated an enrichment of myeloid cell lineage in the GBM tumor microenvironment. Transcript levels of S100A8/S100A9 were found to be independent poor prognostic indicators in GBM. Medium levels of pre-operative and three-month post-operative follow-up serum S100A8 levels predicted poor prognosis in GBM patients who lived beyond median survival. In vitro experiments showed that recombinant S100A8/S100A9 proteins promoted integrin signalling dependent glioma cell migration and invasion up to a threshold level of concentrations. Thus, we have discovered GBM serum marker by iTRAQ and verified by MRM. We also demonstrate interplay between tumor micro and macroenvironment and identified S100A8 as a potential marker with diagnostic and prognostic value in GBM.

High-order radiomics features based on T2 FLAIR MRI predict multiple glioma immunohistochemical features: A more precise and personalized gliomas management

“…Another study reported that S100A4 played a crucial role in neutrophil-promoting tumor progression and S100A4 depletion could increase the effectiveness of anti-VEGF therapy in glioma [56]. S-100 also might be valuable in prognostication of survival for glioma patients [57,58]. The good S-100 prediction performance of T2 FLAIR radiomics in the current study implies its potential in the future applications in gliomas treatment decision-making and effectiveness assessment.…”

Quantitative proteomics reveals reduction of endocytic machinery components in gliomas

“…Pooling of individual controls is a common technique in proteomic analysis and is used for levelling out individual variation to obtain a constant basis for statistical analysis [48]. The use of brain tissue from epileptic patients for control purposes is common and has been proven to be a reliable strategy for the comparison with tumor biopsy material [[38], [39], [40], [41], [42], [43], [44], [45], [46]]. In a similar manner to control, the glioma biopsies were extracted and matched in protein amount to the control sample.…”

“…Samples were collected from patients undergoing surgical removal of gliomas. To match the glioma samples against control tissue, biopsies were collected from patients undergoing surgery for epilepsy, as already described in a number of previous studies [[38], [39], [40], [41], [42], [43], [44], [45], [46]]. Additional control biopsies from white matter were used for quality control by immunoblotting (Fig.…”

Protein Expression Profile in Rat Silicosis Model Reveals Upregulation of PTPN2 and Its Inhibitory Effect on Epithelial-Mesenchymal Transition by Dephosphorylation of STAT3

“…With iTRAQ, the protein expression levels can be compared simultaneously [16]. iTRAQ technology has been applied to muchresearch: To identify prognostic biomarkers for gastric cancer [17]; to reveal potential novel biomarkers for the early diagnosis of acute myocardial infarction within three hours [18]; to identified SAA and ACTB as potential biomarkers in patients with severe hand, foot, and mouth disease (HFMD) [19], to discover glioblastoma serum markers [20], and so on.…”