Westphal Maximillian S, Lee Eunjee, Schadt Eric E, Sholler Giselle S, Zhu Jun
Sema4, 333 Ludlow St., Stamford, CT 06902, USA.
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA.
Cancers (Basel). 2021 Dec 28;14(1):139. doi: 10.3390/cancers14010139.
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.
髓母细胞瘤（MB）是最常见的儿童胚胎性脑肿瘤。目前的共识将MB分为四个分子亚组：音猬因子激活型（SHH）、无翅型激活型（WNT）、3组和4组。MYCN和let-7在MB中起关键作用。因此，我们通过使用ActMiR程序推断MB中miRNA的活性。SHH-MB的MYCN表达高于其他亚组。我们发现，MYCN高表达且let-7活性高与总体生存率较差显著相关，并且这种关联在一个独立的MB数据集中得到了验证。总之，我们的结果表明，let-7活性和MYCN可以将异质性SHH肿瘤进一步分类为预后较好和较差的亚型，这为SHH-MB的个性化治疗方案提供了关键信息。通过比较两种SHH-MB预后亚型与复合扰动谱之间的表达差异，我们确定FGFR抑制剂是预后较差亚型的SHH-MB患者的一种潜在治疗选择。
