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Imaging mass spectrometry identifies prognostic ganglioside species in rodent intracranial transplants of glioma and medulloblastoma.

ABSTRACT: Matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (MALDI-MSI) allows us to investigate the distribution of lipid molecules within tissues. We used MALDI-MSI to identify prognostic gangliosides in tissue sections of rat intracranial allografts of rat glioma and mouse intracranial xenografts of human medulloblastoma. In the healthy adult rodent brain, GM1 and GD1 were the main types of glycolipids. Both gangliosides were absent in both intracranial transplants. The ganglioside GM3 was not present in the healthy adult brain but was highly expressed in rat glioma allografts. In combination with tandem mass spectrometry GM3 (d18:1/C24:0) was identified as the most abundant ganglioside species in the glioma allotransplant. By contrast, mouse xenografts of human medulloblastoma were characterized by prominent expression of the ganglioside GM2 (d18:0/C18:0). Together, these data demonstrate that tissue-based MALDI-MSI of gangliosides is able to discriminate between different brain tumors and may be a useful clinical tool for their classification and grading.

SUBMITTER: Ermini L

PROVIDER: S-EPMC5413052 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Imaging mass spectrometry identifies prognostic ganglioside species in rodent intracranial transplants of glioma and medulloblastoma.

Ermini Leonardo L Morganti Elena E Post Alexander A Yeganeh Behzad B Caniggia Isabella I Leadley Michael M Faria Claudia C CC Rutka James T JT Post Martin M

PloS one 20170502 5

Matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (MALDI-MSI) allows us to investigate the distribution of lipid molecules within tissues. We used MALDI-MSI to identify prognostic gangliosides in tissue sections of rat intracranial allografts of rat glioma and mouse intracranial xenografts of human medulloblastoma. In the healthy adult rodent brain, GM1 and GD1 were the main types of glycolipids. Both gangliosides were absent in both intracranial transplants. The gang ...[more]

PMID: 28463983

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Project description:BackgroundDistal cholangiocarcinoma is an aggressive malignancy with a dismal prognosis. Diagnostic and prognostic biomarkers for distal cholangiocarcinoma are lacking. The aim of the present study was to identify differentially expressed proteins between distal cholangiocarcinoma and normal bile duct samples.MethodsA workflow utilizing discovery mass spectrometry and verification by parallel reaction monitoring was used to analyze surgically resected formalin-fixed, paraffin-embedded samples from distal cholangiocarcinoma patients and normal bile duct samples. Bioinformatic analysis was used for functional annotation and pathway analysis. Immunohistochemistry was performed to validate the expression of thrombospondin-2 and investigate its association with survival.ResultsIn the discovery study, a total of 3057 proteins were identified. Eighty-seven proteins were found to be differentially expressed (q < 0.05 and fold change ≥ 2 or ≤ 0.5); 31 proteins were upregulated and 56 were downregulated in the distal cholangiocarcinoma samples compared to controls. Bioinformatic analysis revealed an abundance of differentially expressed proteins associated with the tumor reactive stroma. Parallel reaction monitoring verified 28 proteins as upregulated and 18 as downregulated in distal cholangiocarcinoma samples compared to controls. Immunohistochemical validation revealed thrombospondin-2 to be upregulated in distal cholangiocarcinoma epithelial and stromal compartments. In paired lymph node metastases samples, thrombospondin-2 expression was significantly lower; however, stromal thrombospondin-2 expression was still frequent (72%). Stromal thrombospondin-2 was an independent predictor of poor disease-free survival (HR 3.95, 95% CI 1.09-14.3; P = 0.037).ConclusionSeveral proteins without prior association with distal cholangiocarcinoma biology were identified and verified as differentially expressed between distal cholangiocarcinoma and normal bile duct samples. These proteins can be further evaluated to elucidate their biomarker potential and role in distal cholangiocarcinoma carcinogenesis. Stromal thrombospondin-2 is a potential prognostic marker in distal cholangiocarcinoma.

Project description:Abstract Considering the high expression of B7-H3 (CD276) on diffuse intrinsic pontine glioma (DIPG) and preliminary evidence that repeated locoregional delivery of CAR T cells to patients with CNS tumors was feasible and tolerable, we open the phase 1 trial BrainChild-03 (NCT04185038). Children with DIPG in Dose Regimen 1 received 40 intraventricular B7H3CAR doses, with the two patients enrolling post-progression surviving >400 days from initial CAR T infusion. To evaluate for immune and tumor responses that may correlate with clinical and radiographic evaluations, we performed targeted proteomic analysis on serial CSF and serum biospecimens. MRM-MS is a targeted mass spectrometry that provides sensitive measurement of proteins in cancer tissues and fluids. In 2 patients with longitudinal biospecimens, we identified 50 CSF and 59 serum proteins above level of detection. In general, there were fewer serum fluctuations compared to the CSF, supporting that intracranial delivery provides local immune activation. Sharp fluctuations of several immunoregulatory peptides were measured in the CSF at pre and post infusion timepoints, including BCL10, CXCL13, TIM-3, ICOSLG, and PD-L2. Notably, several analytes tracked consistently in the CSF of both patients, including markers of macrophage maturation and immune cell recruitment, including CD14, CD163, CD44, CSF-1, CXCL13 and VCAM-1. B7-H3 was detected in the CSF and serum of both patients. S005, who progressed on protocol therapy, had a sharp increase in B7-H3 in the CSF during Course 2, while S008, who had clinical improvement on protocol therapy, had consistently lower B7-H3 present. Notably, serum B7-H3 steadily declined in both patients over time, with the exception of a transient increase in S005 between Courses 4 and 5. Future work for all enrolled patients with DIPG will explore the correlation of these targeted proteomic measurements with clinical end points for potential use as markers of efficacy of therapy or adverse events.

Dataset Information

Imaging mass spectrometry identifies prognostic ganglioside species in rodent intracranial transplants of glioma and medulloblastoma.

Publications

Imaging mass spectrometry identifies prognostic ganglioside species in rodent intracranial transplants of glioma and medulloblastoma.

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