Asparagine synthetase is a predictive biomarker of L-asparaginase activity in ovarian cancer cell lines.
Asparagine synthetase is a predictive biomarker of L-asparaginase activity in ovarian cancer cell lines.
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DOI：
10.1158/1535-7163.mct-08-0589
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发表时间：
2008-10
影响因子：
5.7
通讯作者：
Weinstein JN
中科院分区：
文献类型：
--
作者：
Lorenzi PL;Llamas J;Gunsior M;Ozbun L;Reinhold WC;Varma S;Ji H;Kim H;Hutchinson AA;Kohn EC;Goldsmith PK;Birrer MJ;Weinstein JN
我们最近利用RNA干扰技术证明了L-天冬酰胺酶(L-天冬酰胺酶)的化疗活性与天冬酰胺合成酶(ASNS)在NCI-60细胞系的卵巢亚群中的表达呈负相关是有原因的。为了确定这种关系是否会在更大、更多样化的卵巢细胞系中持续存在，我们现在已经使用微阵列和分支DNA RNA分析检测了ASNS mRNA的表达，使用电化学发光免疫分析检测了ASNS蛋白的表达，并使用MTS法检测了L-天冬氨酸天冬氨酸的活性。与我们之前的发现相反，L-天冬氨酸活性与ASNS mRNA表达只有微弱的相关性；对于微阵列数据，皮尔逊相关系数为r=−0.21，对于分支DNA RNA分析，r=−0.39，后者仅有轻微的统计学意义(p=0.047，单尾)。液相免疫分析法检测ASNS蛋白的表达显示出更强的相关性，r=−0.65(p=0.0014，单尾)。我们得出结论，免疫分析法检测ASNS蛋白的表达是预测L-天冬氨酸在卵巢癌细胞系中活性的一个强有力的单变量预测因子。这些发现为临床评价ASNS蛋白表达作为预测L-天冬氨酸在卵巢癌中活性的生物标志物提供了理论基础。
We recently used RNAi to demonstrate that a negative correlation of L-asparaginase (L-ASP) chemotherapeutic activity with asparagine synthetase (ASNS) expression in the ovarian subset of the NCI-60 cell line panel is causal. To determine whether that relationship would be sustained in a larger, more diverse set of ovarian cell lines, we have now measured ASNS mRNA expression using microarrays and a branched-DNA RNA assay, ASNS protein expression using an electrochemiluminescent immunoassay, and L-ASP activity using an MTS assay on nineteen human ovarian cancer cell lines. Contrary to our previous findings, L-ASP activity was only weakly correlated with ASNS mRNA expression; Pearson’s correlation coefficients were r = −0.21 for microarray data and r = −0.39 for the branched-DNA RNA assay, with just the latter being marginally statistically significant (p = 0.047, one-tailed). ASNS protein expression measured by liquid phase immunoassay exhibited a much stronger correlation, r = −0.65 (p = 0.0014, one-tailed). We conclude that ASNS protein expression measured by immunoassay is a strong univariate predictor of L-ASP activity in ovarian cancer cell lines. These findings provide rationale for clinical evaluation of ASNS protein expression as a predictive biomarker of L-ASP activity in ovarian cancer.