Opposite patterns of association of TWIST1 expression with patient survival in SHH and Group 4 medulloblastoma

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Abstract Purpose Twist1 is a transcription factor that regulates embryonic development, stemness, and differentiation, and can also stimulate initiation of tumorigenesis in peripheral solid cancers. However, its role in central nervous system tumors, including medulloblastoma (MB), the main type of malignant brain cancer that afflicts children, remains poorly understood. Here, we examined expression of Twist1, and its potential significance in prognosis, in different histological variants and molecular subgroups of MB. Methods Gene expression data for TWIST1 and corresponding overall survival (OS) of patients was analyzed in 612 MB samples using a previously described dataset. A cross-sectional analysis of Twist1 protein content in 24 MB tumor samples from patients was carried out by immunohistochemistry. Results TWIST1 transcript levels were higher in classic MB compared to desmoplastic tumors. Within samples with classic histology, higher TWIST1 expression was associated with a longer OS. Tumors in the SHH subgroup had lower TWIST1 expression compared to all other subgroups, and Group 4 showed lower expression than WNT tumors. In Group 4 MB, higher TWIST1 levels were associated with shorter OS, whereas patients with SHH tumors and higher TWIST1 levels showed longer OS. Twist1 protein was detectable in part of classic and LCA MB tumors belonging to the SHH, WNT or Group 3/4 subgroups. Conclusion We found opposite patterns of association between TWST1 and patient survival in Group 4 and SHH MB subgroups. Our results highlight the importance of stratifying tumors by molecular subgroup and histological classification when exploring novel potential biomarkers and therapeutic targets in MB.

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