A 71-gene signature of TRAIL sensitivity in cancer cells
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Updated: May 28, 2026

Discovery of Driver Genes in Colorectal HT29-derived Cancer Stem-Like Tumorspheres
Published on: July 22, 2020
Jun-Jie Chen1, Steen Knudsen, Wiktor Mazin
1Division of Therapeutic Proteins, Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
Abstract:
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.
Insights
Researchers identified a 71-gene signature that predicts cancer cell sensitivity to TNF-related apoptosis-inducing ligand (TRAIL) therapy. This discovery could improve the clinical use of TRAIL for cancer treatment.
Area of Science:
- Molecular Biology
- Cancer Research
- Immunology
Background:
- TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in cancer cells, showing therapeutic promise.
- Cancer cell resistance to TRAIL limits its clinical efficacy.
- Predictive biomarkers are needed to identify patients likely to respond to TRAIL-based therapies.
Purpose of the Study:
- To identify gene expression profiles associated with TRAIL sensitivity in cancer cells.
- To develop a predictive signature for TRAIL responsiveness.
- To explore the role of interferon (IFN) and MHC genes in TRAIL sensitivity.
Main Methods:
- Analysis of genome-wide mRNA expression profiles from the NCI60 cancer cell line panel.
- Differential gene expression analysis comparing TRAIL-sensitive versus TRAIL-resistant cell lines.
- Validation of the identified gene signature in independent test sets of human cancer cell lines.
Main Results:
- A 71-gene signature was identified, with higher expression in TRAIL-sensitive cell lines.
- This 71-gene signature accurately predicted TRAIL sensitivity across multiple cell line datasets.
- The signature is enriched for interferon-induced genes and MHC genes; IFN-γ treatment enhanced TRAIL-induced apoptosis.
Conclusions:
- A 71-gene expression signature can predict cancer cell sensitivity to TRAIL.
- Interferon-induced and MHC genes play a significant role in TRAIL response.
- This signature holds potential for clinical evaluation in predicting tumor response to TRAIL-related therapies.
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