Farnebo Lovisa, Jerhammar Fredrik, Vainikka Linda, Grénman Reidar, Norberg-Spaak Lena, Roberg Karin
Division of Otorhinolaryngology, University Hospital, SE-58185 Linköping, Sweden.
Oncol Rep. 2008 Aug;20(2):453-61.
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.
本研究旨在建立一种结合蛋白质和基因变化多种因素的方法，以预测头颈部鳞状细胞癌（HNSCC）细胞系的放射敏感性。在9种HNSCC细胞系中，蛋白质表达量和基因改变类型被转化为一个评分系统，称为负点数。使用蛋白质印迹的光密度分析对14种参与生长控制和/或凋亡的蛋白质的表达进行定量。将印迹与肌动蛋白进行比对，并根据蛋白质表达量（0 - 3分）将其标准化为正常口腔角质形成细胞，分为四组。p53基因的突变分为三组，每个突变给予1分。由于每个细胞系都有已知的内在放射敏感性，因此可以进行多变量统计计算，以选择与放射敏感性相关性最强的因素组合。所研究因素的最强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，P < 0.0001）。没有单一因素与内在放射敏感性有显著相关性。由于只有当两个或更多因素组合时才与内在放射敏感性有显著相关性，我们得出结论，像负点数这样的方法对于预测治疗反应是必要的。我们提出了一种结合多种因素的新方法，能够预测HNSCC细胞系的放射敏感性。
