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,...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-06-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-020-07048-0 |
| _version_ | 1818249126101385216 |
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| author | Sharon Y. Y. Low Nurfahanah Bte Syed Sulaiman Enrica E. K. Tan Lee Ping Ng Chik Hong Kuick Kenneth T. E. Chang Phua Hwee Tang Ru Xin Wong Wen Shen Looi David C. Y. Low Wan Tew Seow |
| author_facet | Sharon Y. Y. Low Nurfahanah Bte Syed Sulaiman Enrica E. K. Tan Lee Ping Ng Chik Hong Kuick Kenneth T. E. Chang Phua Hwee Tang Ru Xin Wong Wen Shen Looi David C. Y. Low Wan Tew Seow |
| author_sort | Sharon Y. Y. Low |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T15:31:32Z |
| format | Article |
| id | doaj.art-eec7ce7d6fa34396ad49a6487f00eb67 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-12T15:31:32Z |
| publishDate | 2020-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-eec7ce7d6fa34396ad49a6487f00eb672022-12-22T00:20:07ZengBMCBMC Cancer1471-24072020-06-0120111010.1186/s12885-020-07048-0Cerebrospinal fluid cytokines in metastatic group 3 and 4 medulloblastomaSharon Y. Y. Low0Nurfahanah Bte Syed Sulaiman1Enrica E. K. Tan2Lee Ping Ng3Chik Hong Kuick4Kenneth T. E. Chang5Phua Hwee Tang6Ru Xin Wong7Wen Shen Looi8David C. Y. Low9Wan Tew Seow10Neurosurgical Service, KK Women’s and Children’s HospitalDepartment of Neurosurgery, National Neuroscience InstitutePaediatric Haematology/Oncology Service, KK Women’s and Children’s HospitalNeurosurgical Service, KK Women’s and Children’s HospitalDepartment of Pathology and Laboratory Medicine, KK Women’s and Children’s HospitalVIVA-KKH Paediatric Brain and Solid Tumours LaboratoryDepartment of Diagnostic and Interventional Imaging, KK Women’s and Children’s HospitalDepartment of Radiation OncologyDepartment of Radiation OncologyNeurosurgical Service, KK Women’s and Children’s HospitalNeurosurgical Service, KK Women’s and Children’s HospitalAbstract 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.http://link.springer.com/article/10.1186/s12885-020-07048-0Cerebrospinal fluidCytokinesMedulloblastomaMetastasis |
| spellingShingle | Sharon Y. Y. Low Nurfahanah Bte Syed Sulaiman Enrica E. K. Tan Lee Ping Ng Chik Hong Kuick Kenneth T. E. Chang Phua Hwee Tang Ru Xin Wong Wen Shen Looi David C. Y. Low Wan Tew Seow Cerebrospinal fluid cytokines in metastatic group 3 and 4 medulloblastoma BMC Cancer Cerebrospinal fluid Cytokines Medulloblastoma Metastasis |
| title | Cerebrospinal fluid cytokines in metastatic group 3 and 4 medulloblastoma |
| title_full | Cerebrospinal fluid cytokines in metastatic group 3 and 4 medulloblastoma |
| title_fullStr | Cerebrospinal fluid cytokines in metastatic group 3 and 4 medulloblastoma |
| title_full_unstemmed | Cerebrospinal fluid cytokines in metastatic group 3 and 4 medulloblastoma |
| title_short | Cerebrospinal fluid cytokines in metastatic group 3 and 4 medulloblastoma |
| title_sort | cerebrospinal fluid cytokines in metastatic group 3 and 4 medulloblastoma |
| topic | Cerebrospinal fluid Cytokines Medulloblastoma Metastasis |
| url | http://link.springer.com/article/10.1186/s12885-020-07048-0 |
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