Asparagine synthetase is a predictive biomarker of L-asparaginase activity in ovarian cancer cell lines.
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.
Genomics and Bioinformatics Group, Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA.
Philip L
PL
Lorenzi
Jenny
J
Llamas
Michele
M
Gunsior
Laurent
L
Ozbun
William C
WC
Reinhold
Sudhir
S
Varma
Helen
H
Ji
Hijoo
H
Kim
Amy A
AA
Hutchinson
Elise C
EC
Kohn
Paul K
PK
Goldsmith
Michael J
MJ
Birrer
John N
JN
Weinstein
D001215:Asparaginase / Q000378:metabolism*; D001217:Aspartate-Ammonia Ligase / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D016172:DNA Fingerprinting; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D001215:Asparaginase; D001217:Aspartate-Ammonia Ligase