期刊
MOLECULAR ONCOLOGY
卷 15, 期 12, 页码 3691-3705出版社
WILEY
DOI: 10.1002/1878-0261.12996
关键词
gene signature; predictive biomarkers; trabectedin
类别
资金
- Spanish Group for Research on Sarcoma (GEIS)
- PharmaMar
- National Institute of Health Carlos III (ISCIII) [CD20/00155]
- ISCIII-Red de Biobancos [PT17/0015/0041]
This study identified a six-gene predictive signature of trabectedin efficacy in advanced soft-tissue sarcomas. By evaluating 118 genes involved in DNA damage repair, potential biomarkers of trabectedin sensitivity or resistance were defined. Targeting some genes of this signature may enhance trabectedin efficacy in treatment.
Predictive biomarkers of trabectedin represent an unmet need in advanced soft-tissue sarcomas (STS). DNA damage repair (DDR) genes, involved in homologous recombination or nucleotide excision repair, had been previously described as biomarkers of trabectedin resistance or sensitivity, respectively. The majority of these studies only focused on specific factors (ERCC1, ERCC5, and BRCA1) and did not evaluate several other DDR-related genes that could have a relevant role for trabectedin efficacy. In this retrospective translational study, 118 genes involved in DDR were evaluated to determine, by transcriptomics, a predictive gene signature of trabectedin efficacy. A six-gene predictive signature of trabectedin efficacy was built in a series of 139 tumor samples from patients with advanced STS. Patients in the high-risk gene signature group showed a significantly worse progression-free survival compared with patients in the low-risk group (2.1 vs 6.0 months, respectively). Differential gene expression analysis defined new potential predictive biomarkers of trabectedin sensitivity (PARP3 and CCNH) or resistance (DNAJB11 and PARP1). Our study identified a new gene signature that significantly predicts patients with higher probability to respond to treatment with trabectedin. Targeting some genes of this signature emerges as a potential strategy to enhance trabectedin efficacy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据