Asparagine synthetase is a predictive biomarker of L-asparaginase activity in ovarian cancer cell lines

摘要

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.