Immunohistochemical detection of 5-hydroxymethylcytosine as a prognostic biomarker in non-WNT/Non-SHH medulloblastomas

Although reduced levels of global 5-hydroxymethylcytosine (5hmC) have been observed in medulloblastomas (MBs), it remains unclear whether immunohistochemical (IHC) evaluation of 5hmC can serve as a prognostic biomarker for patients with MB. We performed IHC staining using a 5hmC antibody on a cohort of 114 pediatric MBs, including 69 non-WNT/non-SHH MBs. The 5hmC staining score was evaluated using a 9-point scale based on both the staining intensity and the percentage positive cells. We found that a low 5hmC staining score (< 5 points) was associated with poor outcomes in patients with non-WNT/non-SHH MB (both P < 0.001). Multivariate Cox regression analyses demonstrated the 5hmC staining score was an independent prognostic predictor for progression-free survival (P < 0.001) and overall survival (P = 0.004) in patients with non-WNT/non-SHH MB. Both the receiver operating characteristic curves and calibration curves demonstrated the excellent performance of the nomogram models established based on the Cox regression models. The high predictive accuracy of the nomogram models was confirmed in a validation cohort comprising 32 patients with non-WNT/non-SHH MB. In conclusion, IHC evaluation of 5hmC may serve as a cost-effective and readily accessible approach for the prognostic stratification of patients with non-WNT/non-SHH MB.