Dataset Information

Proteomics of tumor and serum samples from isocitrate dehydrogenase-wildtype glioblastoma patients: is the detoxification of reactive oxygen species associated with shorter survival?

ABSTRACT: Proteomics has been little used for the identification of novel prognostic and/or therapeutic markers in isocitrate dehydrogenase (IDH)-wildtype glioblastoma (GB). In this study, we analyzed 50 tumor and 30 serum samples from short- and long-term survivors of IDH-wildtype GB (STS and LTS, respectively) by data-independent acquisition mass spectrometry (DIA-MS)-based proteomics, with the aim of identifying such markers. DIA-MS identified 5422 and 826 normalized proteins in tumor and serum samples, respectively, with only three tumor proteins and 26 serum proteins displaying significant differential expression between the STS and LTS groups. These dysregulated proteins were principally associated with the detoxification of reactive oxygen species (ROS). In particular, GB patients in the STS group had high serum levels of malate dehydrogenase 1 (MDH1) and ribonuclease inhibitor 1 (RNH1) and low tumor levels of fatty acid-binding protein 7 (FABP7), which may have enabled them to maintain low ROS levels, counteracting the effects of the first-line treament with radiotherapy plus concomitant and adjuvant temozolomide. A blood score built on the levels of MDH1 and RNH1 expression was found to be an independent prognostic factor for survival based on the serum proteome data for a cohort of 96 IDH-wildtype GB patients. This study highlights the utility of circulating MDH1 and RNH1 biomarkers for determining the prognosis of patients with IDH-wildtype GB. Furthermore, the pathways driven by these biomarkers, and the tumor FABP7 pathway, may constitute promising therapeutic targets for blocking ROS detoxification to overcome resistance to chemoradiotherapy in potential GB STS.

INSTRUMENT(S): Bruker Daltonics timsTOF series

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Serum, Glioblastoma Cell

DISEASE(S): Glioblastoma

SUBMITTER: Catherine Guette

LAB HEAD: Anne Clavreul

PROVIDER: PXD045714 | Pride | 2024-07-04

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	GLIO-1-2_Slot1-1_1_268.d.7z	Other
	GLIO-10-2_Slot1-10_1_277.d.7z	Other
	GLIO-100_020315_Slot2-25_1_2854.d.7z	Other
	GLIO-101_020352_Slot2-26_1_2855.d.7z	Other
	GLIO-102_020302_Slot2-27_1_2856.d.7z	Other

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Publications

Proteomics of tumor and serum samples from isocitrate dehydrogenase-wildtype glioblastoma patients: is the detoxification of reactive oxygen species associated with shorter survival?

Clavreul Anne A Guette Catherine C Lasla Hamza H Rousseau Audrey A Blanchet Odile O Henry Cécile C Boissard Alice A Cherel Mathilde M Jézéquel Pascal P Guillonneau François F Menei Philippe P Lemée Jean-Michel JM

Molecular oncology 20240527 11

Proteomics has been little used for the identification of novel prognostic and/or therapeutic markers in isocitrate dehydrogenase (IDH)-wildtype glioblastoma (GB). In this study, we analyzed 50 tumor and 30 serum samples from short- and long-term survivors of IDH-wildtype GB (STS and LTS, respectively) by data-independent acquisition mass spectrometry (DIA-MS)-based proteomics, with the aim of identifying such markers. DIA-MS identified 5422 and 826 normalized proteins in tumor and serum samples ...[more]

PMID: 38803161

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Project description:We probed the mechanism of cross-regulation of osmotic and heat stress responses by characterizing the effects of high osmolarity (0.3M vs. 0.0M NaCl) and temperature (43oC vs. 30oC) on the transcriptome of Escherichia coli K12 using E. coli Genome 2 Array (Affymetrix, Inc.). Independent array hybridizations were carried out for 3 biological replicates (independent cultures). Total RNA was extracted using a hot phenol-chloroform method. cDNA synthesis, fragmentation and labeling, and washing and scanning of E. coli GeneChip Arrays were performed according to the instructions of the manufacturer (Affymetrix Technical Manual, Affymetrix, Inc., USA). Labeled cDNA was hybridized to E. coli Genome 2 Array (Affymetrix, Inc.). Independent array hybridizations were carried out for 3 biological replicates (independent cultures) of each condition. A number of genes in the SoxRS and OxyR oxidative stress regulons were up-regulated by high osmolarity, high temperature, and/or by the combination of both stresses. This result could account for cross-protection of osmotic stress against oxidative stress. The trehalose biosynthetic genes were induced by both stresses, in accord with the proposed protective role of this disaccharide against thermal and oxidative damage. Experiment Overall Design: E. coli K12 strain NCM3722 cultures were grown with aeration in K medium containing 10 or 20 mM glucose. To impose osmotic stress, the osmolarity of the medium was increased to 0.64 osm by supplementation with 0.3 M NaCl. Because E. coli is a methionine auxotroph above 42oC the K medium cultures were supplemented with 0.5 mM methionine. Glycine betaine (GB) was added to the high osmolarity media to a final concentration of 1 mM. Cells taken from a single colony on LB agar were inoculated into 1ml liquid LB and grown to saturation at 37oC, then 0.05 ml were inoculated into i) K medium, 0.5 mM methionine, 10 mM glucose; ii) K medium, 0.5 mM methionine, 10 mM glucose, 0.3 M NaCl; and iii) K medium, 0.5 mM methionine, 10 mM glucose, 0.3 M NaCl, 1 mM GB. The cultures were grown to saturation at 30oC and 43oC, and sub-cultured once into the same medium and grown at the same temperatures as before. Exponentially growing cells form these cultures were then inoculated into Erlenmeyer flasks (starting OD600nm 0.05) containing 40 ml of the same medium, and incubated in the same salt and temperature conditions as used previously, except that the glucose concentration was increased to 20 mM. When the cells reached OD600nm of 0.4-0.5 (~3 doublings), 25 ml were added to a 2.5 ml mixture of cold 95% ethanol and 5% phenol to preserve RNA. The cells were cooled briefly on ice, immediately harvested by centrifugation (4oC), and the pellet was frozen on dry ice. The six different growth conditions used were: C1 - 30oC, no NaCl; C2: 30oC, 0.3 M NaCl; C3: 30oC, 0.3 M NaCl, 1 mM GB; C4: 43oC, no NaCl; C5: 43oC, 0.3 M NaCl; C6: 43oC, 0.3 M NaCl, 1 mM GB.

Project description:Acute respiratory distress syndrome (ARDS) carries about a 50 percent mortality and is frequently associated with an infection (sepsis). Life-support treatment with mechanical ventilation rescues many patients, although superimposed infection or multiple organ failure can result in death. The outcome of a patient developing sepsis highly depends on the degree of pre-existing inflammation prior to the infection. In this study, we describe each stage of the inflammation process using a transcriptional approach and an animal model. Femelle C57BL6/J mice received an intraveinous oleic acid injection to induce an acute lung injury. PBMC expression patterns have been analyzed using a 9900 cDNA mouse microarray (MUSV29K). Our gene-expression analysis revealed marked changes in the immune and inflammatory response metabolic pathways, notably lipid metabolism and transcription. The early pro-inflammatory stage (1H-1H30) is characterized by the release of immune response and activation of inflammatory mechanisms. Later (3H-4H), the immune cells migrate into inflamed tissues through interaction with vascular endothelial cells. Finally, at late stages of lung inflammation (18H-24H), metabolism is deeply disturbed. Highly expressed pro-inflammatory cytokines activate transcription of many genes as well as lipid metabolism. This global overview of critical events occuring during lung inflammation is essential to understand infectious pathologies such as sepsis where inflammation and infection are interwined. From now on, it becomes possible to isolate the impact of a pathogen at the transcriptional level from the global gene expression modifications resulting from the infection associated with the inflammation. Also, our work allowed to identify genes involved in the response to inflammation. Among those, several may be potential target for gene therapy. Wild-type femelle C57Bl/6J mice, 7 weeks old, were obtained from Charles River and housed in a specific pathogen-free animal facility. We studied 39 mice divided into 6 groups. Each group was identified according to the incubation time: 1H, 1H30, 3H, 4H, 18H and 24H. The 1H group was made up of 6 mice (2 physiological serum and 4 OA); the 1H30 group was made up of 8 mice (2 physiological serum and 6 OA); the 3H group was made up of 7 mice (2 physiological serum and 5 OA); the 4H group was made up of 6 mice (2 physiological serum and 4 OA); the 18H group was made up of 6 mice (2 physiological serum and 4 OA); the 24H group was made up of 6 mice (2 physiological serum and 4 OA). Several RNA samples have been hybridized on 2 filters consisting in technical replicates. Data normalized by quantile without adjustment on physiological serum linked on Series record.

Dataset Information

Proteomics of tumor and serum samples from isocitrate dehydrogenase-wildtype glioblastoma patients: is the detoxification of reactive oxygen species associated with shorter survival?

Dataset's files

Publications

Proteomics of tumor and serum samples from isocitrate dehydrogenase-wildtype glioblastoma patients: is the detoxification of reactive oxygen species associated with shorter survival?

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