通过竞争性RT-PCR检测神经母细胞瘤中生长抑素受体2型基因表达与患者生存和生长抑素受体铟-111-戊戊肽显像有关。

C. Orlando, C. C. Raggi, L. Bagnoni, R. Sestini, V. Briganti, G. La Cava, G. Bernini, G. Tonini, M. Pazzagli, M. Serio, M. Maggi
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引用次数: 31

摘要

我们之前报道过人类神经母细胞瘤细胞系和原发性神经母细胞瘤肿瘤表达2型生长抑素(sst2)受体基因mRNA的量是可变的。我们还发现高水平的sst2表达与患者生存呈正相关。我们回顾性研究了49例原发性神经母细胞瘤。为了检测和测量sst2 mRNA的表达,我们在竞争性PCR的基础上建立了定量RT-PCR。在可能的情况下,用竞争性PCR法测定MYCN的拷贝数。结果,。我们发现,与其他阶段相比,晚期神经母细胞瘤(IV期)中检测到的sst2 mRNA水平最低(P< 0.005)。sst2高表达(bbb7 x 10(7)个分子/微RNA)患者的累积生存期优于sst2低表达患者(P < 0.0005)。在N-myc扩增分层后,sst2的预测独立值(P= 0.005)仍然保留。最后,我们通过111in - penteotide成像验证了肿瘤样本中体外sst2基因表达与体内sst2蛋白半定量测定呈正相关(P < 0.01)。结论我们的数据表明,sst2 mRNA的测定可以作为预测神经母细胞瘤预后的相关工具,独立于MYCN扩增。
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Somatostatin receptor type 2 gene expression in neuroblastoma, measured by competitive RT-PCR, is related to patient survival and to somatostatin receptor imaging by indium -111-pentetreotide.
BACKGROUND We previously reported that human neuroblastoma cell lines and primary neuroblastoma tumors expressed a variable amount of mRNA for type 2 somatostatin (sst2) receptor gene. We also found that high level of sst2 expression were positively related to patient survival. PROCEDURE We studied retrospectively 49 primary neuroblastomas. To detect and measure sst2 mRNA expression we developed a quantitative RT-PCR based on competitive PCR. When possible the number of MYCN copies was also measured with competitive PCR. RESULTS;. We found that the lowest level of sst2 mRNA was detected in advanced stages of neuroblastomas (stage IV) when compared with the other stages (P< 0.005). Patients with high levels of sst2 expression (>7 x 10(7) molecules/microg RNA) had a cumulative survival better than those with low sst2 expression (P < 0.0005). This predictive independent value of sst2 (P= 0.005) is retained after stratification for N-myc amplification. Finally we verified that the ex vivo sst2 gene expression in tumor samples was positively related (P < 0.01) to the in vivo semiquantitative determination of sst2 protein, assessed by 111In-pentetreotide imaging. CONCLUSIONS Our data indicate that the measurement of sst2 mRNA measurement could represent a relevant tool in the prediction of neuroblastoma outcome, independently from MYCN amplification.
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