Nagata T, Takahashi Y, Asai S, Ishii Y, Mugishima H, Suzuki T, Chin M, Harada K, Koshinaga S, Ishikawa K
Department of Pharmacology, Department of Pediatrics, Department of Pediatric Surgery, Nihon University School of Medicine, 30-1 Oyaguchikami-cho, Itabashi-ku, Tokyo, 173-0032, Japan.
J Surg Res. 2000 Aug;92(2):267-75. doi: 10.1006/jsre.2000.5918.
The biological behavior of neuroblastomas detected through mass screening (MS, </=1 year of age) and that of mass screening-negative later-presenting (MSN, >1 year of age) neuroblastomas have been reported to differ in many studies. To investigate the biological differences between these two groups, we analyzed the differences in mRNA profiles.
We analyzed the mRNA profiles of MS and MSN neuroblastomas using differential display, and cloned and sequenced the bands differentially expressed between these two groups. Using the RNA analysis by polymerase chain reaction (RNA-PCR) method, the relative amount of mRNA in tumor tissue in each sample was measured. Associations between relative amount of mRNA and clinical and genetic variables related to patient prognosis and the effect of the level of mRNA expression on survival probability were investigated using statistical methods.
Using differential display and RNA-PCR, we found that the mRNA for the human homologue of the yeast cdc10 gene (hCDC10) identified in Saccharomyces cerevisiae was expressed at a higher level in the MS group of patients than in the MSN group of patients (0.554 +/- 0.197 for MS neuroblastoma, n = 24 and 0.244 +/- 0.179 for MSN neuroblastoma, n = 10, P < 0.01), and this difference was suggested to be independent of the histologic subtype of tumor. A high level of hCDC10 mRNA expression in neuroblastomas (relative amount of hCDC10 mRNA > 0.35) was also suggested to be associated with younger age at diagnosis (</=1 year of age, P < 0.01), favorable clinical stage (I, II, and IVs, P < 0. 01), and favorable histology in the Shimada classification (P < 0. 01), whereas a low level of hCDC10 mRNA expression (relative amount of hCDC10 mRNA </=0.35) was suggested to be associated with the progression of clinical stage (P < 0.01) and N-myc gene amplification (>1 copy, P < 0.05). Patients with neuroblastomas with a high level of hCDC10 mRNA expression were suggested to have a better prognosis than those with a low level of hCDC10 mRNA expression (P < 0.01).
A high level of hCDC10 mRNA expression in neuroblastomas may be associated with favorable clinical and biological characteristics, and the expression of hCDC10 mRNA in neuroblastomas may affect the clinical and biological characteristics of this type of tumor.
多项研究报道，通过大规模筛查（MS，年龄≤1岁）检测出的神经母细胞瘤与大规模筛查阴性、后期发病（MSN，年龄>1岁）的神经母细胞瘤的生物学行为存在差异。为了研究这两组之间的生物学差异，我们分析了mRNA谱的差异。
我们使用差异显示技术分析了MS和MSN神经母细胞瘤的mRNA谱，并对两组之间差异表达的条带进行了克隆和测序。采用聚合酶链反应（RNA-PCR）法进行RNA分析，测定每个样本肿瘤组织中mRNA的相对含量。使用统计方法研究mRNA相对含量与患者预后相关的临床和遗传变量之间的关联，以及mRNA表达水平对生存概率的影响。
通过差异显示和RNA-PCR，我们发现，在酿酒酵母中鉴定出的酵母cdc10基因的人类同源物（hCDC10）的mRNA在MS组患者中的表达水平高于MSN组患者（MS神经母细胞瘤为0.554±0.197，n = 24；MSN神经母细胞瘤为0.244±0.179，n = 10，P<0.01），并且这种差异被认为与肿瘤的组织学亚型无关。神经母细胞瘤中高水平的hCDC10 mRNA表达（hCDC10 mRNA相对含量>0.35）还被认为与诊断时年龄较小（≤1岁，P<0.01）、临床分期良好（I、II和IVs期，P<0.01）以及岛田分类中组织学良好（P<0.01）相关，而低水平的hCDC10 mRNA表达（hCDC10 mRNA相对含量≤0.35）则被认为与临床分期进展（P<0.01）和N-myc基因扩增（>1拷贝，P<0.05）相关。hCDC10 mRNA表达水平高的神经母细胞瘤患者的预后被认为优于hCDC10 mRNA表达水平低的患者（P<0.01）。
神经母细胞瘤中高水平的hCDC10 mRNA表达可能与良好的临床和生物学特征相关，并且hCDC10 mRNA在神经母细胞瘤中的表达可能影响这类肿瘤的临床和生物学特征。
