Major finding: FSTL5 is a prognostic biomarker that predicts poor outcome in MB.
Approach: Transcriptome and DNA copy number analyses were performed on primary MB.
Impact: FSTL5 screening will improve stratification and prognostication of MB patients.
Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Treatment regimens cure up to 75% of patients, yet leave many with cognitive and/or endocrine dysfunction. Based upon genomic and immunohistochemical analysis, four distinct molecular variants of MB have been identified: WNT (wingless), SHH (sonic hedgehog), group C, and group D. In contrast to WNT and SHH, the prognosis of non-WNT/non-SHH tumors is poor and the underlying genetic changes remain unknown. Hoping to identify new molecular biomarkers of non-WNT/non-SHH tumors that may aid in the stratification of high- versus low-risk patients, Remke and colleagues performed transcriptome and copy number analyses on primary MB. Their findings delineated genetic markers associated with the four MB subgroups and noted the association of group C and particularly group D tumors with advanced disease and poor prognosis. Interestingly, the gene for follistatin-like protein 5, FSTL5, was overexpressed in group C and some group D tumors and was significantly associated with reduced progression-free and overall survival across all disease variants. Little is known about the function of FSTL5, a member of the activin/follistatin system, and only a few reports link the gene family to cancer-related processes. Significantly, the current findings conclude that FSTL5 is a reliable independent prognostic marker for MB. Addition of FSTL5 to the four-class molecular staging system enhances prediction accuracy for non-WNT/non-SHH MB and will inform the development of more effective and less toxic treatment regimens for MB patients.
Note: Research Watch is written by Cancer Discovery Science Writers. Readers are encouraged to consult the original articles for full details.
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