Number of Negative Points:: A novel method for predicting radiosensitivity in head and neck tumor cell lines
Number of Negative Points:: A novel method for predicting radiosensitivity in head and neck tumor cell lines
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DOI：
10.3892/or_00000028
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发表时间：
2008-08-01
期刊：
影响因子：
4.2
通讯作者：
Roberg, Karin
中科院分区：
文献类型：
--
作者：
Farnebo, Lovisa;Jerhammar, Fredrik;Roberg, Karin
本研究旨在建立一种结合蛋白质和遗传变化的多因素预测头颈部鳞状细胞癌（HNSCC）细胞系放射敏感性的方法。在9个HNSCC细胞系中，蛋白质表达的数量和遗传改变的类型被翻译成一个点系统，称为负点数。使用Western印迹的光密度评估来定量参与生长控制和/或凋亡的14种蛋白质的表达。将印迹调整为肌动蛋白，并标准化为正常口腔角质形成细胞，根据表达的蛋白质的量（0-3分）将其分为四组。将p53基因突变分为三组，每种突变一个点。由于每个细胞系都具有已知的固有放射敏感性，因此可以进行多元统计计算以选择与放射敏感性相关性最强的因素组合。研究因素中最强的相关性是表皮生长因子受体、生存素和剪接位点/错义p53突变的组合（R=0.990和P < 0.0001）。无单一因素与固有放射敏感性显著相关。由于只有当两个或两个以上的因素相结合时，才能实现与内在放射敏感性的显着相关性，因此我们得出结论，如阴性点数的方法对于预测治疗反应是必要的。我们提出了一种新的方法来联合收割机的因素，使预测的放射敏感性的HNSCC细胞系。
The present study was aimed at establishing a method that combines multiple factors of protein and genetic changes that enables prediction of radiosensitivity in the head and neck squamous cell carcinoma (HNSCC) cell lines. In nine HNSCC cell lines, the quantity of protein expression and the type of genetic alterations were translated into a point system, called the Number of Negative Points. The expression of 14 proteins involved in growth control and/or apoptosis was quantified using a densitometric assessment of Western blots. The blots were adjusted to actin and standardised to normal oral keratinocytes classifying them into four groups depending on the amount of protein expressed (0-3 points). Mutations of the p53 gene were classified into three groups and each mutation was given one point. Since the cell lines each had a known intrinsic radiosensitivity, a multivariate statistical calculation could then be performed to select for the combination of factors having the strongest correlation to radiosensitivity. The strongest correlation of the investigated factors was the combination of epidermal growth factor receptor, survivin and splice site/missense p53 mutations (R=0.990 and P < 0.0001). No single factor had a significant correlation to the intrinsic radiosensitivity. Since a significant correlation to the intrinsic radiosensitivity was achieved only when two or more factors were combined, we conclude that a method such as the Number of Negative Points is necessary for prediction of treatment response. We present a novel method to combine factors which enables the prediction of radiosensitivity of HNSCC cell lines.