A 71-gene signature of TRAIL sensitivity in cancer cells.
TNF-related apoptosis inducing ligand (TRAIL) is a promising anticancer agent because of its ability to selectively induce apoptosis in cancer cells but not in most normal cells. However, some cancer cells are resistant to TRAIL cytotoxicity thereby limiting its therapeutic efficacy. Using genome-wide mRNA expression profiles from the NCI60 panel and their differential sensitivities to TRAIL-induced apoptosis, we have identified 71 genes whose expression levels are systemically higher in TRAIL-sensitive cell lines than resistant lines. The elevated expression of the 71 genes was able to accurately predict TRAIL sensitivity in the NCI60 training set and two test sets consisting of a total of 95 human cancer cell lines. Interestingly, the 71-gene signature is dominated by two functionally related gene families-interferon (IFN)-induced genes and the MHC genes. Consistent with this result, treatment with IFN-γ augmented TRAIL-induced apoptosis. The 71-gene signature could be evaluated clinically for predicting tumor response to TRAIL-related therapies.
Division of Therapeutic Proteins, Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
Jun-Jie
JJ
Chen
Steen
S
Knudsen
Wiktor
W
Mazin
Jesper
J
Dahlgaard
Baolin
B
Zhang
D017209:Apoptosis / Q000502:physiology; D014408:Biomarkers, Tumor / Q000235:genetics*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D009369:Neoplasms / Q000235:genetics; D012333:RNA, Messenger; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics*
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D053221:TNF-Related Apoptosis-Inducing Ligand; D007371:Interferon-gamma