Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Laboratorio di Ricerca Oncologica, Orthopedic Institute Rizzoli, Italy.
Eur J Cancer. 2015 Nov;51(17):2624-33. doi: 10.1016/j.ejca.2015.08.020. Epub 2015 Sep 28.
Ewing sarcoma (EWS) is the second most common sarcoma of bone in children and young adults. Patients with disseminated disease at diagnosis or early relapse have a poor prognosis. Our goal was to identify novel predictive biomarkers for these patients, focusing on chemokines, specifically genes involved in the CXCR4-pathway because of their established role in metastasis and tumour growth.
Total RNA isolated from therapy-naïve tumour samples (n=18; panel I) and cell lines (n=21) was used to study expression of CXCR4-pathway related genes and CXCR4 splice variants (CXCR4-2: Small and CXCR4-1: Large) by RT-Q-PCR. Expression levels were correlated to overall survival (OS) and event free survival (EFS). Study results were validated in an independent series of 26 tumour samples (panel II) from therapy-naïve tumour samples.
CXCL12, CXCR4, CXCR7 and CXCL14 were expressed and high CXCR7 and CXCL14 expression showed a positive correlation with EFS and OS and a negative correlation with metastasis development. Both splice variants CXCR4 were expressed in cell lines and tumour samples and CXCR4-1/CXCR4-2 ratio was significantly higher in tumour samples compared to cell lines and correlated with an improved EFS and OS. The results from the test panel were validated in an independent sample panel.
We identified a set of genes involved in CXCR4 signalling that may be used as a marker to predict survival and metastasis development in Ewing sarcoma.
尤文肉瘤（EWS）是儿童和青少年中第二常见的骨肉瘤。在诊断时或早期复发时出现弥散性疾病的患者预后不良。我们的目标是确定这些患者的新的预测性生物标志物，重点关注趋化因子，特别是涉及 CXCR4 通路的基因，因为它们在转移和肿瘤生长中发挥着重要作用。
从未经治疗的肿瘤样本（n=18；面板 I）和细胞系（n=21）中分离总 RNA，用于通过 RT-Q-PCR 研究 CXCR4 通路相关基因和 CXCR4 剪接变体（CXCR4-2：Small 和 CXCR4-1：Large）的表达。表达水平与总生存（OS）和无事件生存（EFS）相关。研究结果在来自未经治疗的肿瘤样本的 26 个肿瘤样本的独立系列（面板 II）中得到验证。
CXCL12、CXCR4、CXCR7 和 CXCL14 表达，高 CXCR7 和 CXCL14 表达与 EFS 和 OS 呈正相关，与转移发展呈负相关。两种剪接变体 CXCR4 在细胞系和肿瘤样本中均有表达，CXCR4-1/CXCR4-2 比值在肿瘤样本中明显高于细胞系，与改善的 EFS 和 OS 相关。测试面板的结果在独立样本面板中得到验证。
我们确定了一组参与 CXCR4 信号的基因，可作为预测尤文肉瘤生存和转移发展的标志物。
