Identification of let-7 miRNA activity as a prognostic biomarker of SHH medulloblastoma

Maximillian S. Westphal, Eunjee Lee, Eric E. Schadt, Giselle S. Sholler, Jun Zhu

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Medulloblastoma (MB) is the most common pediatric embryonal brain tumor. The current consensus classifies MB into four molecular subgroups: sonic hedgehog-activated (SHH), wingless-activated (WNT), Group 3, and Group 4. MYCN and let-7 play a critical role in MB. Thus, we inferred the activity of miRNAs in MB by using the ActMiR procedure. SHH-MB has higher MYCN expression than the other subgroups. We showed that high MYCN expression with high let-7 activity is significantly associated with worse overall survival, and this association was validated in an independent MB dataset. Altogether, our results suggest that let-7 activity and MYCN can further categorize heterogeneous SHH tumors into more and less-favorable prognostic subtypes, which provide critical information for personalizing treatment options for SHH-MB. Comparing the expression differences between the two SHH-MB prognostic subtypes with compound perturbation profiles, we identified FGFR inhibitors as one potential treatment option for SHH-MB patients with the less-favorable prognostic subtype.

Original languageEnglish (US)
Article number139
JournalCancers
Volume14
Issue number1
DOIs
StatePublished - Jan 1 2022

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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