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

Lorenzi, P.L., Llamas, J., Gunsior, M., Ozbun, L., Reinhold, W.C., Varma, S., Ji, H., Kim, H., Hutchinson, A.A., Kohn, E.C., Goldsmith, P.K., Birrer, M.J., Weinstein, J.N.
Journal   Mol Cancer Ther.
Analytes Measured  
Matrix Tested   Cell lysates
Year   2008
Volume   10
Page Numbers   3123-8
Application   Phosphoproteins
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.

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