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Insulin-like growth factor-1 receptor gene expression is associated with survival in breast cancer: a comprehensive analysis of gene copy number, mRNA and protein expression

机译:胰岛素样生长因子-1受体基因表达与乳腺癌的生存有关:基因拷贝数,mRNA和蛋白质表达的全面分析

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摘要

Insulin-like growth factor-1 receptor (IGF1R) plays a key role in the initiation and progression of breast cancer. However, its prognostic relevance to breast cancer patients has long been a matter of debate. In a series of 325 primary invasive breast cancer patients, we performed a comprehensive analysis of IGF1R at the levels of gene copy number, mRNA expression and protein expression. The relationship between the IGF1R status and the clinicopathological characteristics and prognosis was evaluated. IGF1R mRNA levels not only correlated with protein expression, but also significantly associated with several clinicopathological parameters and prognosis of the patients. Patients with low nuclear grade, negative axillary lymph node, positive hormone receptor, negative HER2, negative Ki67 and luminal subtype tumors showed higher level expression of IGF1R mRNA, which was shown to be a significant univariate parameter for both relapse free survival (RFS) and breast cancer specific survival (BCSS) as well as significant multivariate parameter for BCSS. IGF1R protein expression showed an association with a prolonged BCSS in univariate analysis. By contrast, IGF1R gene copy number did not correlated with mRNA and protein expression, and harbored no prognostic value. When studied in breast tumor subtype groups relatively, IGF1R mRNA level was still significantly associated with a better BCSS. Overall, our data indicated a correlation among IGF1R mRNA expression and protein expression in primary breast cancer. In particular, the IGF1R mRNA expression appeared to be a good prognostic marker either in the entire cohort or in the luminal subtype group. These data may serve as background information for IGF1R-targeted therapy.
机译:胰岛素样生长因子1受体(IGF1R)在乳腺癌的发生和发展中起着关键作用。然而,其与乳腺癌患者的预后相关性长期以来一直是争论的问题。在一系列325例原发性浸润性乳腺癌患者中,我们在基因拷贝数,mRNA表达和蛋白质表达水平上对IGF1R进行了全面分析。评估了IGF1R的状态与临床病理特征和预后之间的关系。 IGF1R mRNA水平不仅与蛋白质表达相关,而且与患者的一些临床病理参数和预后显着相关。低核级,腋窝淋巴结阴性,激素受体阳性,HER2阴性,Ki67阴性和管腔亚型肿瘤的患者显示较高水平的IGF1R mRNA表达,这对于无复发生存(RFS)和乳腺癌特异性生存率(BCSS)以及BCSS的重要多元参数。在单变量分析中,IGF1R蛋白表达与BCSS延长有关。相比之下,IGF1R基因拷贝数与mRNA和蛋白表达无关,并且没有预后价值。当在乳腺肿瘤亚型组中进行相对研究时,IGF1R mRNA水平仍与更好的BCSS显着相关。总体而言,我们的数据表明原发性乳腺癌中IGF1R mRNA表达与蛋白表达之间存在相关性。特别是,无论是在整个队列研究中还是在管腔亚型组中,IGF1R mRNA的表达似乎都是良好的预后标志。这些数据可以作为针对IGF1R的疗法的背景信息。

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