Dataset Information

Cerebrospinal fluid cytokines in metastatic group 3 and 4 medulloblastoma.

ABSTRACT:

Background

Metastatic medulloblastoma (MB) portends a poor prognosis. Amongst the 4 molecular subtypes, Group 3 and Group 4 patients have a higher incidence of metastatic disease, especially involving the neuroaxis. At present, mechanisms underlying MB metastasis remain elusive. Separately, inflammation has been implicated as a key player in tumour development and metastasis. Cytokines and their inflammation-related partners have been demonstrated to act on autocrine and, or paracrine pathways within the tumour microenvironment for various cancers. In this study, the authors explore the involvement of cerebrospinal fluid (CSF) cytokines in Group 3 and 4?MB patients with disseminated disease.

Methods

This is an ethics approved, retrospective study of prospectively collected data based at a single institution. Patient clinicpathological data and corresponding bio-materials are collected after informed consent. All CSF samples are interrogated using a proteomic array. Resultant expression data of selected cytokines are correlated with each individual's clinical information. Statistical analysis is employed to determine the significance of the expression of CSF cytokines in Group 3 and 4 patients with metastatic MB versus non-metastatic MB.

Results

A total of 10 patients are recruited for this study. Median age of the cohort is 6.6?years old. Based on Nanostring gene expression analysis, 5 patients have Group 3 as their molecular subtype and the remaining 5 are Group 4. There are 2 non-metastatic versus 3 metastatic patients within each molecular subtype. Proteomic CSF analysis of all patients for both subtypes show higher expression of CCL2 in the metastatic group versus the non-metastatic group. Within the Group 3 subtype, the MYC-amplified Group 3?MB patients with existing and delayed metastases express higher levels of CXCL1, IL6 and IL8 in their CSF specimens at initial presentation. Furthermore, a longitudinal study of metastatic Group 3?MB observes that selected cytokines are differentially expressed in MYC-amplified metastatic Group 3?MB, in comparison to the non-MYC amplified metastatic Group 3?MB patient.

Conclusion

This study demonstrates higher expression of selected CSF cytokines, in particular CCL2, in metastatic Group 3 and 4?MB patients. Although our results are preliminary, they establish a proof-of-concept basis for continued work in a larger cohort of patients affected by this devastating disease.

SUBMITTER: Low SYY

PROVIDER: S-EPMC7296667 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cerebrospinal fluid cytokines in metastatic group 3 and 4 medulloblastoma.

Low Sharon Y Y SYY Bte Syed Sulaiman Nurfahanah N Tan Enrica E K EEK Ng Lee Ping LP Kuick Chik Hong CH Chang Kenneth T E KTE Tang Phua Hwee PH Wong Ru Xin RX Looi Wen Shen WS Low David C Y DCY Seow Wan Tew WT

BMC cancer 20200615 1

<h4>Background</h4>Metastatic medulloblastoma (MB) portends a poor prognosis. Amongst the 4 molecular subtypes, Group 3 and Group 4 patients have a higher incidence of metastatic disease, especially involving the neuroaxis. At present, mechanisms underlying MB metastasis remain elusive. Separately, inflammation has been implicated as a key player in tumour development and metastasis. Cytokines and their inflammation-related partners have been demonstrated to act on autocrine and, or paracrine pa ...[more]

PMID: 32539808

Similar Datasets

Project description:BACKGROUND:Idiopathic intracranial hypertension (IIH) is a neurological disorder characterised by raised cerebrospinal fluid (CSF) pressure in the absence of any intracranial pathology. IIH mainly affects women with obesity between the ages of 15 and 45. Two possible mechanisms that could explain the increased CSF pressure in IIH are excessive CSF production by the choroid plexus (CP) epithelium or impaired CSF drainage from the brain. However, the molecular mechanisms controlling these mechanisms in IIH remain to be determined. METHODS:In vivo ventriculo-cisternal perfusion (VCP) and variable rate infusion (VRI) techniques were used to assess changes in rates of CSF secretion and resistance to CSF drainage in female and male Wistar rats fed either a control (C) or high-fat (HF) diet (under anaesthesia with 20 μl/100 g medetomidine, 50 μl/100 g ketamine i.p). In addition, CSF secretion and drainage were assessed in female rats following treatment with inflammatory mediators known to be elevated in the CSF of IIH patients: C-C motif chemokine ligand 2 (CCL2), interleukin (IL)-17 (IL-17), IL-6, IL-1β, tumour necrosis factor-α (TNF-α), as well as glucocorticoid hydrocortisone (HC). RESULTS:Female rats fed the HF diet had greater CSF secretion compared to those on control diet (3.18 ± 0.12 μl/min HF, 1.49 ± 0.15 μl/min control). Increased CSF secretion was seen in both groups following HC treatment (by 132% in controls and 114% in HF) but only in control rats following TNF-α treatment (137% increase). The resistance to CSF drainage was not different between control and HF fed female rats (6.13 ± 0.44 mmH2O min/μl controls, and 7.09 ± 0.26 mmH2O min/μl HF). and when treated with CCL2, both groups displayed an increase in resistance to CSF drainage of 141% (controls) and 139% (HF) indicating lower levels of CSF drainage. CONCLUSIONS:Weight loss and therapies targeting HC, TNF-α and CCL2, whether separately or in combination, may be beneficial to modulate rates of CSF secretion and/or resistance to CSF drainage pathways, both factors likely contributing to the raised intracranial pressure (ICP) observed in female IIH patients with obesity.

Dataset Information

Cerebrospinal fluid cytokines in metastatic group 3 and 4 medulloblastoma.

Background

Methods

Results

Conclusion

Publications

Cerebrospinal fluid cytokines in metastatic group 3 and 4 medulloblastoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets