Lorenzi Philip L, Llamas Jenny, Gunsior Michele, Ozbun Laurent, Reinhold William C, Varma Sudhir, Ji Helen, Kim Hijoo, Hutchinson Amy A, Kohn Elise C, Goldsmith Paul K, Birrer Michael J, Weinstein John N
Genomics and Bioinformatics Group, Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA.
Mol Cancer Ther. 2008 Oct;7(10):3123-8. doi: 10.1158/1535-7163.MCT-08-0589.
We recently used RNA interference to show 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 19 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 evaluation of ASNS protein expression as a predictive biomarker of clinical L-ASP activity in ovarian cancer.
我们最近利用RNA干扰技术证明，在NCI - 60细胞系面板的卵巢亚组中，L - 天冬酰胺酶（L - ASP）化疗活性与天冬酰胺合成酶（ASNS）表达呈负相关，且这种相关性具有因果关系。为了确定这种关系在更大、更多样化的卵巢细胞系中是否依然成立，我们现在使用微阵列和分支DNA RNA检测法测量了19种人卵巢癌细胞系的ASNS mRNA表达，使用电化学发光免疫检测法测量了ASNS蛋白表达，并使用MTS检测法测量了L - ASP活性。与我们之前的研究结果相反，L - ASP活性与ASNS mRNA表达仅呈弱相关；微阵列数据的Pearson相关系数r = -0.21，分支DNA RNA检测法的r = -0.39，只有后者在统计学上具有微弱的显著性（P = 0.047，单尾）。通过液相免疫检测法测量的ASNS蛋白表达呈现出更强的相关性（r = -0.65；P = 0.0014，单尾）。我们得出结论，通过免疫检测法测量的ASNS蛋白表达是卵巢癌细胞系中L - ASP活性的一个强有力的单变量预测指标。这些发现为评估ASNS蛋白表达作为卵巢癌临床L - ASP活性的预测生物标志物提供了理论依据。
