Zhao Han-Guang, Ren Si-Kang, Zhou Wen-Tao, Liu Zhi-Ming, Wang Lei-Ming, Tian Yong-Ji, Zhao Fu
Department of Pediatric Neurosurgery, Beijing Neurosurgical Institute, Capital Medical University, 119 south 4th Ring West Road, Fengtai District, Beijing, 100070, China.
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Sci Rep. 2025 May 5;15(1):15633. doi: 10.1038/s41598-025-00052-z.
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.
尽管在髓母细胞瘤（MBs）中已观察到整体5-羟甲基胞嘧啶（5hmC）水平降低，但5hmC的免疫组织化学（IHC）评估是否可作为MB患者的预后生物标志物仍不清楚。我们使用5hmC抗体对114例儿童MBs进行了IHC染色，其中包括69例非WNT/非SHH MBs。基于染色强度和阳性细胞百分比，使用9分制评估5hmC染色评分。我们发现，非WNT/非SHH MB患者中5hmC染色评分低（<5分）与预后不良相关（两者P<0.001）。多变量Cox回归分析表明，5hmC染色评分是非WNT/非SHH MB患者无进展生存期（P<0.001）和总生存期（P = 0.004）的独立预后预测指标。受试者工作特征曲线和校准曲线均显示基于Cox回归模型建立的列线图模型具有出色的性能。在一个由32例非WNT/非SHH MB患者组成的验证队列中证实了列线图模型的高预测准确性。总之，5hmC的IHC评估可能是一种经济高效且易于采用的方法，用于非WNT/非SHH MB患者的预后分层。
