Dataset Information

RNAseq Analysis in glioblastoma cells treated with Mepazine

ABSTRACT: Glioblastoma cells were treated with vehicle (DMSO) or mepazine (MPZ, 20 μM, 4 hours) and prepared for RNAseq according to ActiveMotif standard procedure. The list of differentially expressed genes from DESeq2 output was selected based on 10% adjusted p-value level and FDR of 0.1.

ORGANISM(S): Homo sapiens

PROVIDER: GSE139018 | GEO | 2019/10/18

REPOSITORIES: GEO

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Dataset's files

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			Action	DRS
		Other
	GSE139018_DESeq2_results_allgenes.csv.gz	Csv
	GSE139018_DESeq2_results_diffgenes.csv.gz	Csv
	GSE139018_RNAseq_stats.xlsx	Xlsx
	GSE139018_featureCounts.txt.gz	Txt

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Project description:Unbiased proteomics of human cerebrospinal fluid (CSF) has been used successfully to identify biomarkers of Amyotrophic Lateral Sclerosis (ALS). However, high abundance proteins mask the presence of lower abundance proteins that may hold valuable diagnostic and prognostic use. Developments in mass spectrometry proteomic data acquisition methods therefore hold promise for improved protein depth and more sensitive biomarker discovery. In this study, mass spectrometry with library-free data-independent acquisition (DIA) was used to compare the CSF proteome of 40 people with ALS, 15 healthy controls and 8 people with mimicking conditions. Qthen quantified protein groups were subsequently correlated with clinical variables. Univariate analysis identified 7 proteins significantly upregulated in ALS vs healthy controls, and 9 with altered abundance in ALS vs mimicking conditions (FDR <0.1). Elevated Chitotriosidase 1 (CHIT1) was common to both comparisons and showed strong correlation with disease progression rate (Pearson r =0.41, FDR-adjusted p = 0.035), but no association with survival (Pearson correlation and Kaplan-Meier survival analysis). Ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1; upregulated in ALS vs healthy controls) showed a stronger correlation with disease progression rate (Pearson r = 0.53, FDR-adjusted p = 0.003) and significant association with survival in Kaplan Meier analysis (log rank p = 0.013) but no independent effect in proportional hazards models. Weighted correlation network analysis was then used to identify functionally relevant modules of proteins. One module, enriched for inflammatory functions, was strongly associated with age at disease onset (Pearson r = 0.58, FDR-adjusted p = 0.005) and survival (Hazard Ratio 1.78, FDR = 0.065), and a second module, enriched for endoplasmic reticulum proteins, negatively correlated with disease progression rate (r = -0.42, FDR-adjusted p =0.109). This study confirms that UCHL1 is strongly associated with disease progression and survival, and highlights potential of inflammatory and endoplasmic reticulum proteins to provide prognostic biomarker potential.

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RNAseq Analysis in glioblastoma cells treated with Mepazine

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