研究概要
CD200 是神经母细胞瘤中一个强有力的负向预后生物标志物,与免疫抑制性肿瘤微环境和化疗耐药相关。它代表了治疗分层的一个有前景的候选指标,以及改善高危患者预后的潜在治疗靶点。
研究思路结论见上方概要
目的
高危神经母细胞瘤预后较差,而免疫抑制性糖蛋白CD200在该疾病中的作用仍不明确。在本研究中,我们探讨了CD200表达的作用。
方法
我们回顾性分析了45例神经母细胞瘤标本中CD200的表达情况,采用免疫组化(IHC)方法。评估了其与临床病理特征、患者生存及TIL(肿瘤浸润淋巴细胞)(TILs)密度的关联。在高危亚组中检测了化疗期间CD200表达的变化。通过siRNA介导的沉默技术在SH-SY5Y和IMR-32神经母细胞瘤细胞系中体外评估了CD200在化疗敏感性中的功能作用。
结果
高CD200表达与晚期疾病、复发和较差的总生存期显著相关(5年OS:57.3% vs. 低CD200组100%,p = 0.007)。高CD200肿瘤显示CD4 + 和CD8 + T细胞浸润显著减少。在高危患者中,化疗后持续高表达或CD200表达升高与100%的复发率和死亡率相关。在体外,CD200沉默显著增强了顺铂的细胞毒性作用。
展开英文摘要原文
PURPOSE
High-risk neuroblastomas carry a poor prognosis, and the role of the immunosuppressive glycoprotein CD200 in this disease remains unclear. In this study, we investigated the role of CD200 expression.
METHODS
We retrospectively analyzed CD200 expression in 45 neuroblastoma specimens using immunohistochemistry (IHC). Its association with clinicopathological features, patient survival, and tumor-infiltrating lymphocytes (TILs) density was evaluated. Changes in CD200 expression during chemotherapy were examined in the high-risk subgroup. The functional role of CD200 in chemosensitivity was assessed in vitro using siRNA-mediated silencing in SH-SY5Y and IMR-32 neuroblastoma cell lines.
RESULTS
High CD200 expression was significantly associated with advanced-stage disease, recurrence, and poor overall survival (5-year OS: 57.3% vs. 100% in low-CD200, p = 0.007). High-CD200 tumors showed significantly reduced infiltration of CD4 + and CD8 + T cells. In high-risk patients, persistently high or increased post-chemotherapy CD200 expression was correlated with 100% recurrence and mortality. In vitro, CD200 silencing significantly enhanced the cytotoxic effects of cisplatin.
CONCLUSION
CD200 is a strong negative prognostic biomarker in neuroblastoma, associated with an immunosuppressive tumor microenvironment and chemoresistance. It represents a promising candidate for treatment stratification and a potential therapeutic target for improving outcomes in high-risk patients.
论文信息
- 作者
- Kuroda Y、Zuo S、Terai T、Miyao S、Nakamura K、Kanehiro H、Yoshida M、Hatakeyama T
- 第一作者单位
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634- 8522, Japan.Japan
- 通讯作者单位
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634- 8522, Japan. m-sho@naramed-u.ac.jp.Japan
- 期刊
- Pediatric surgery international2026 Jan 22