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CTGF expression is indicative of better survival rates in patients with medulloblastoma

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Abstract

Medulloblastoma (MB) is the most frequent malignant brain tumor in children and it is subgrouped into 4 entities (SHH, WNT, Group 3, and Group 4). Molecular pathways involved in these different subgroups still are evolving and can be of clinical relevance to therapy. The YAP1-CTGF axis is known to regulate cell proliferation, differentiation, and cell death; however, its role in MB is poorly explored. We aimed to investigate the role of YAP1 gene in the MB SHH cell line DAOY and evaluate cell proliferation, doubling time and 3D spheroids invasion and its consequence on CTGF regulation. We assessed CTGF expression from 22 children with MB. Lastly, we validated our findings through in silico analysis in large cohorts dataset of patients. We observed an increased invasion rate of DAOY cells and CTGF downregulation under YAP1 knockdown (p < 0.0001). Additionally CTGF is overexpressed in MB with extensive nodularity subtype and an indicative of higher survival rates in pediatric MB (p < 0.05). Interestingly, no difference of CTGF expression was observed between molecular subgroups. These results provide new evidence of CTGF as a potential prognostic marker for MB, corroborating to the role of YAP1 in restricting MB cell.

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Funding

This work was supported by FAPESP grant number 2017/06511–8, 2014/19976–0 and 2014/20341–0.

Author information

G.A.V.C. planned and conducted all experiments, performed the in silico analysis, drafted, and critically read the manuscript. R.C.P.L conducted the overall survival analysis, helped to design the study, and critically read the manuscript. T.A.M., helped to review the design of the study, performed the in silico analysis, and critically read the manuscript. C.A.S. critically read the manuscript, M.B. critically read the manuscript and helped to design the study. L.G.T. provided patient samples and critically read the manuscript. E.T.V. critically read the manuscript.

Correspondence to Gustavo Alencastro Veiga Cruzeiro.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This research was submitted to and approved by the HC/FMRP-USP Research Ethics Committee (CAAE no 37206114.1.0000.5440) no 15509/2016.

Informed consent

All samples were obtained after receiving informed consent from all participants included in the study.

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