Dataset Information

Determination of a tumor-promoting microenvironment in recurrent medulloblastoma: a multi-omics study of cerebrospinal fluid

ABSTRACT: Molecular characterization of medulloblastoma (MB) cell origin and properties is the basis for a well-defined classification system. However, limited data is available regarding the MB tumor microenvironment. Here we present a mass spectrometry-based multi-omics study of cerebrospinal fluid (CSF) from recurrent MB patients. A group of age-matched patients without a neoplastic disease was used as control cohort. Proteome profiling identified several characteristic tumor markers and revealed a strong prevalence of anti-inflammatory and tumor-promoting proteins characteristic for alternatively polarized myeloid cells in MB samples. The up-regulation of ADAMTS1, GAP43 and GPR37 indicated hypoxia in CSF of MB patients. This notion was independently supported by metabolomics, demonstrating up-regulation of tryptophan, methionine, serine and lysine, all of which have been described to be induced upon hypoxia in CSF. The beta-oxidation promoting lipid hormone 12,13-DiHOME was found strongly upregulated, potentially promoting a metabolic shift supporting drug resistance and stem cell properties of MB cells.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cerebrospinal Fluid

DISEASE(S): Medulloblastoma

SUBMITTER: Christopher Gerner

LAB HEAD: Christopher Gerner

PROVIDER: PXD018226 | Pride | 2020-06-01

REPOSITORIES: Pride

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Determination of a Tumor-Promoting Microenvironment in Recurrent Medulloblastoma: A Multi-Omics Study of Cerebrospinal Fluid.

Reichl Bernd B Niederstaetter Laura L Boegl Thomas T Neuditschko Benjamin B Bileck Andrea A Gojo Johannes J Buchberger Wolfgang W Peyrl Andreas A Gerner Christopher C

Cancers 20200526 6

Molecular classification of medulloblastoma (MB) is well-established and reflects the cell origin and biological properties of tumor cells. However, limited data is available regarding the MB tumor microenvironment. Here, we present a mass spectrometry-based multi-omics pilot study of cerebrospinal fluid (CSF) from recurrent MB patients. A group of age-matched patients without a neoplastic disease was used as control cohort. Proteome profiling identified characteristic tumor markers, including F ...[more]

PMID: 32466393

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Project description:The foundation for integrating mass spectrometry (MS)-based proteomics into systems medicine is to develop standardized start-to-finish and fit-for-purpose workflows for clinical specimens. An essential step in this pursuit is to highlight common ground in a diverse landscape of different sample preparation techniques and LC-MS setups with the aim to explore differences and potential confounding factors as well as to identify areas for improvement with a direct practical benefit. With the aim to benchmark and improve current best practices among the proteomics MS laboratories of the CLINSPECT-M consortium we performed two consecutive round robin studies with full freedom to operate in terms of sample preparation and MS measurements. The six participating study partners were provided with two clinically relevant sample matrices: plasma, and cerebrospinal fluid (CSF). In the first round each laboratory applied their current best practice protocol for the respective matrix, covering laboratory-specific sample proteolysis, liquid chromatography, and MS measurement procedure. All resulting MS files were analyzed centrally by a standardized pipeline. Based on the achieved results and following a fully transparent exchange of all lab-specific protocols within the consortium, each laboratory could improve their methods before measuring the same samples in a second acquisition round. The results of both measurement time points are compared with respect to identifications (IDs), data completeness, retention time and quantitative precision as well as inter-laboratory reproducibility. For instance, the number of identified protein groups was increased on average by 14% for CSF and 5% for plasma from first to second measurement round across participants resulting in a median overlap number of 579 protein groups for CSF and 246 IDs for plasma across setups. The individual performances of participating study centers and the inter-laboratory reproducibility were improved in the second measurement, emphasizing the effect and importance of expert-driven exchange of best practices. In total, the study not only clearly demonstrates the beneficial effect of sharing knowledge and expertise for direct practical improvements but also highlights tendencies such as common limits of detection or preferable preparation strategies.

			Action	DRS
	CSF_MB_1_1.mzML	Mzml
	CSF_MB_1_1.mzid.gz	Mzid
	CSF_MB_1_1.pride.mgf.gz	Mgf
	CSF_MB_1_1.raw	Raw
	CSF_MB_1_2.mzML	Mzml