Proteins inform survival-based differences in patients with glioblastoma

Abstract

Background Improving the care of patients with glioblastoma (GB) requires accurate and reliable predictors of patient prognosis. Unfortunately, while protein markers are an effective readout of cellular function, proteomics has been underutilized in GB prognostic marker discovery. Methods For this study, GB patients were prospectively recruited and proteomics discovery using liquid chromatography–mass spectrometry analysis (LC-MS/MS) was performed for 27 patients including 13 short-term survivors (STS) (≤10 months) and 14 long-term survivors (LTS) (≥18 months). Results Proteomics discovery identified 11 941 peptides in 2495 unique proteins, with 469 proteins exhibiting significant dysregulation when comparing STS to LTS. We verified the differential abundance of 67 out of these 469 proteins in a small previously published independent dataset. Proteins involved in axon guidance were upregulated in STS compared to LTS, while those involved in p53 signaling were upregulated in LTS. We also assessed the correlation between LS MS/MS data with RNAseq data from the same discovery patients and found a low correlation between protein abundance and mRNA expression. Finally, using LC-MS/MS on a set of 18 samples from 6 patients, we quantified the intratumoral heterogeneity of more than 2256 proteins in the multisample dataset. Conclusions These proteomic datasets and noted protein variations present a beneficial resource for better predicting patient outcome and investigating potential therapeutic targets.

A Prognostic Model for Glioblastoma Patients Treated With Standard Therapy Based on a Prospective Cohort of Consecutive Non-Selected Patients From a Single Institution

“…Despite advances in histological and molecular subtypes, the factors included in prognostic models are mainly clinical observations such as PS, age and corticosteroid treatment (4,(9)(10)(11)(12). Tissue biomarkers and data from imaging techniques have been suggested as independent prognostic factors (6,25,26), and may contribute to improvement of future prognostic models.…”

Large-Scale Phosphoproteomic Study of Arabidopsis Membrane Proteins Reveals Early Signaling Events in Response to Cold

“…A minimum of two peptides identified per protein was considered as a confident identification of that protein. The peak intensities, from both the phosphorylated and proteotypic non-phosphorylated peptides generated from Skyline-Daily, were normalized using the EigenMS normalization method [ 175 , 176 , 177 ] in the ProteoMM R-Bioconductor package [ 178 ]. All raw data files were deposited in the Japan Proteome Standard Repository/Database (jPOST; JPST000993, Kyoto, Japan).…”

SETMAR Shorter Isoform: A New Prognostic Factor in Glioblastoma

“…snRNP70 is an early key regulator of 5’ splice site selection known to be methylated by SETMAR both in vitro and in cellulo ( 7 ) but its potential action on SETMAR mRNAs has never been studied. The snRNP70 protein has been recently found to be enriched in long survivor patients with GB ( 25 ). PTN is a growth factor implicated in brain differentiation ( 26 ) and its gene contains a SETMAR binding site in the 5’UTR ( 27 ).…”

“…Finally, we found a negative correlation between snRNP70 and α-S-SETMAR in short survivors (p=0.047; r=-0.695, Spearman’s test). A proteomic study related to GB overexpressed proteins and survival has been recently published ( 25 ). In line with our results, both OLIG2 and PTN amounts do not vary between short and long survivors, whereas snRNP70 appears to belong to the 393 proteins significantly upregulated in long survivors.…”

“…Second, these are two different cancers (bladder versus GB) and NONO is reported to have different prognosis impacts depending on the cancer considered (19). Finally, we would like to stress that the correlation between the expression levels of a mRNA and of its corresponding protein need to be systematically verified (25). From this point of view, transcriptomics studies are very likely to lead to misinterpretations.…”