Gene isoforms as expression-based biomarkers predictive of drug response in vitro.
Nat Commun
; 8(1): 1126, 2017 10 24.
Article
de En
| MEDLINE
| ID: mdl-29066719
ABSTRACT
Next-generation sequencing technologies have recently been used in pharmacogenomic studies to characterize large panels of cancer cell lines at the genomic and transcriptomic levels. Among these technologies, RNA-sequencing enable profiling of alternatively spliced transcripts. Given the high frequency of mRNA splicing in cancers, linking this feature to drug response will open new avenues of research in biomarker discovery. To identify robust transcriptomic biomarkers for drug response across studies, we develop a meta-analytical framework combining the pharmacological data from two large-scale drug screening datasets. We use an independent pan-cancer pharmacogenomic dataset to test the robustness of our candidate biomarkers across multiple cancer types. We further analyze two independent breast cancer datasets and find that specific isoforms of IGF2BP2, NECTIN4, ITGB6, and KLHDC9 are significantly associated with AZD6244, lapatinib, erlotinib, and paclitaxel, respectively. Our results support isoform expressions as a rich resource for biomarkers predictive of drug response.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Pharmacogénétique
/
Tests de criblage d'agents antitumoraux
/
Marqueurs biologiques
/
Isoformes de protéines
/
Tumeurs
Type d'étude:
Prognostic_studies
/
Risk_factors_studies
Limites:
Humans
Langue:
En
Journal:
Nat Commun
Sujet du journal:
BIOLOGIA
/
CIENCIA
Année:
2017
Type de document:
Article