年龄对儿童髓母细胞瘤预后的影响及其肿瘤微环境分析

目的分析不同年龄段髓母细胞瘤患者生存率，探讨肿瘤微环境中免疫细胞浸润对预后的影响及其与年龄的相关性，并筛选年龄相关免疫调节分子。方法对公共数据库中的队列进行研究，使用Kaplan-Meier曲线进行生存分析，根据年龄不同，利用MCPcounter对免疫细胞绝对丰度进行量化，同时筛选年龄相关免疫调节分子，寻找影响低龄髓母细胞瘤预后的危险因素。结果髓母细胞瘤患者的生存率随年龄的减少而降低，0~3岁的婴幼儿期髓母细胞瘤患者生存率在队列所有病例中最低。婴幼儿期患儿肿瘤微环境中的效应免疫细胞CD8+T细胞、细胞毒性淋巴细胞、中性粒细胞、B淋巴细胞显著低于其他年龄段患儿，肿瘤相关纤维母细胞、单核细胞、内皮细胞显著高于其他年龄段患儿。CXCR4的高表达与效应免疫细胞浸润呈负相关，与肿瘤相关细胞呈正相关，这些免疫细胞与髓母细胞瘤预后密切相关。结论低龄引起髓母细胞瘤不良预后与CXCR4高表达介导的肿瘤微环境重塑密切相关。

Objective To analyze the prognosis of patients with medulloblastoma at different ages, and to explore the influence of immune cell infiltration on prognosis and the correlation with age, and screen age-related immune regulatory molecules. Methods In the study, cohorts from public database were studied through informatic analysis, Kaplan-meier curves were used for survival analysis, and MCPcounter was used to quantify the absolute abundance of immune cells in different ages. Meanwhile, age-related different expression genes were screened, and the effects of different expression genes on immune cell infiltration were analyzed. Results The survival rate of patients aged 0-3 years was the lowest among all patients in the cohort. The number of CD8+T cells, cytotoxic lymphocytes, neutrophils and B lineage in the tumor microenvironment of infants were significantly lower than other age groups, while the number of tumor-associated fibroblasts, monocyte lineage and endothelial cells were significantly higher than other age groups. The expression of CXCR4 was negatively correlated with the infiltration of effector immune cells and positively correlated with tumor-associated cells, which were closely related to the prognosis of medulloblastoma. Conclusion The poor prognosis of infants medulloblastoma is closely related to the remodeling of tumor microenvironment mediated by CXCR4 expression.