Laboratory of Genomics and Molecular Biology, CIPE, Hospital A.C. Camargo, Brazil.
Eur J Cancer. 2011 Dec;47(18):2715-22. doi: 10.1016/j.ejca.2011.05.024. Epub 2011 Jun 22.
Wilms tumour (WT) is a paediatric kidney tumour, composed of blastemal, epithelial and stromal cells, with a relapse rate of approximately 15%. Long-term survival for patients with relapse remains approximately 50%. Current clinical and molecular research is directed towards identifying prognostic factors to define the minimal and intensive therapy for successful treatment of children with low and high risk of relapse, respectively. Blastemal component presents a high level of aggressiveness and responsiveness to chemotherapy. To identify molecular prognostic markers that are predictive of chemotherapy sensitivity in tumour relapse, blastemal-enriched samples from stage III and IV WT, from patients with relapse or without relapse, were analysed for 4608 human genes immobilised on a customised cDNA platform. These analyses revealed 69 differentially expressed genes, and the top nine genes were further evaluated by qRT-PCR in the initial WT samples. TSPAN3, NCOA6, CDO1, MPP2 and MCM2 were confirmed to be down-regulated in relapse WT, and TSPAN3 and NCOA6 were also validated in an independent sample group. Protein expression of MCM2 and NCOA6 were observed in 38% (13 out of 34) and 28% (9 out of 32), respectively, of independent stage III and IV WT blastema samples, without association with relapse. However, a significant association between MCM2 positive staining and chemotherapy as first treatment suggests the involvement of MCM2 with drug metabolism in WT blastemal cells.
威尔姆斯瘤（WT）是一种儿科肾肿瘤，由胚细胞瘤、上皮细胞和基质细胞组成，复发率约为 15%。复发患者的长期生存率仍约为 50%。目前的临床和分子研究旨在确定预后因素，以分别为低复发风险和高复发风险的儿童定义最小和强化治疗。胚细胞瘤成分具有较高的侵袭性和对化疗的反应性。为了确定预测肿瘤复发时化疗敏感性的分子预后标志物，对来自 III 期和 IV 期 WT 的复发或未复发患者的胚细胞瘤富集样本进行了分析，这些样本针对固定在定制 cDNA 平台上的 4608 个人类基因。这些分析显示了 69 个差异表达的基因，其中前 9 个基因在初始 WT 样本中通过 qRT-PCR 进一步评估。在复发的 WT 中，TSPAN3、NCOA6、CDO1、MPP2 和 MCM2 被证实下调，并且 TSPAN3 和 NCOA6 在独立样本组中也得到了验证。在 38%（34 例中的 13 例）和 28%（32 例中的 9 例）的独立 III 期和 IV 期 WT 胚细胞瘤样本中观察到 MCM2 和 NCOA6 的蛋白表达，与复发无关。然而，MCM2 阳性染色与首次化疗之间存在显著关联表明 MCM2 参与 WT 胚细胞瘤细胞的药物代谢。
