RT Journal Article
SR Electronic
T1 Biomarker identification for statin sensitivity of cancer cell lines
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 215756
DO 10.1101/215756
A1 Vineet K. Raghu
A1 Colin H. Beckwitt
A1 Katsuhiko Warita
A1 Alan Wells
A1 Panayiotis V. Benos
A1 Zoltán N. Oltvai
YR 2017
UL http://biorxiv.org/content/early/2017/11/07/215756.abstract
AB Statins are potent cholesterol reducing drugs that have been shown to reduce tumor cell proliferation in vitro and tumor growth in animal models. Moreover, retrospective human cohort studies demon-strated decreased cancer-specific mortality in patients taking statins. We previously implicated membrane E-cadherin expression as both a marker and mechanism for resistance to atorvastatin-mediated growth suppression of cancer cells; however, a transcriptome-profile-based biomarker signature for statin sensitivity has not yet been reported. Here, we utilized transcriptome data from fourteen NCI-60 cancer cell lines and their statin dose-response data to produce gene expression signatures that identify statin sensitive and resistant cell lines. We experimentally confirmed the validity of the identified biomarker signature in an independent set of cell lines and extended this signature to generate a proposed statin-sensitive subset of tumors listed in the TCGA database. Finally, we predicted drugs that would synergize with statins and found several predicted combination therapies to be experimentally confirmed. The combined bioinformatics-experimental approach described here can be used to generate an initial biomarker sensitivity for statin therapy.