Abstract
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.
Overview
- The study investigates the use of immunohistochemical (IHC) evaluation of 5-hydroxymethylcytosine (5hmC) as a prognostic biomarker for pediatric medulloblastomas (MBs).
- The study focuses on non-WNT/non-SHH MBs, using a cohort of 114 pediatric MBs and evaluating the 5hmC staining score on a 9-point scale.
- The primary objective is to determine whether IHC evaluation of 5hmC can serve as a prognostic biomarker for patients with non-WNT/non-SHH MB, and to establish a nomogram model for prognostic stratification.
Comparative Analysis & Findings
- A low 5hmC staining score (< 5 points) was associated with poor outcomes in patients with non-WNT/non-SHH MB, with a significant difference seen in both progression-free survival (P < 0.001) and overall survival (P = 0.004).
- The 5hmC staining score was an independent prognostic predictor for both progression-free survival and overall survival in patients with non-WNT/non-SHH MB, as demonstrated by multivariate Cox regression analyses.
- Nomogram models established based on Cox regression models demonstrated excellent performance in both the training and validation cohorts, with high predictive accuracy and calibration curves.
Implications and Future Directions
- The study suggests that 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.
- Future studies could explore the potential role of 5hmC in other types of pediatric brain tumors and examine its relationship with other biomarkers and clinical variables.
- The establishment of a diagnostic test for 5hmC could provide a valuable tool for clinicians, allowing for more tailored treatment strategies and improved patient outcomes.