ena-STUDY-Centrum Medyczne Ksztalcenia Podyplomowego-27-09-2018-12:23:28:022-200
Redefining the practical utility of blood transcriptome biomarkers in inflammatory bowel diseases
Background and Aims. The study investigates the practical utility of whole blood gene expression profiling to diagnose inflammatory bowel diseases (IBDs).Methods. The discovery cohorts included 102 and 51 pediatric IBD patients and controls, and 95 and 46 adult IBD patients and controls, respectively. The replication cohorts included 447 and 76 pediatric IBD patients and controls, and 271 and 108 adult IBD patients and controls, respectively. In the discovery phase, RNA samples extracted from whole peripheral blood were analyzed using RNA-Seq and the predictive values of selected biomarkers were validated using quantitative (q)PCR.Results. 15 differentially expressed transcripts (adjusted P = 0.05) were selected from the discovery sequencing datasets. The Receiver Operating Characteristic curves and area under the curve (ROC-AUC) in replication analyses showed high discriminative power (AUC range, 0.91–0.98) for eleven mRNAs in pediatric patients with active IBD. By contrast, the AUC-ROC values ranged from 0.63 to 0.75 in comparison of inactive pediatric IBDs and active/inactive adult IBDs, indicating a lack of discriminative power. The best multi-mRNA diagnostic classifier showed moderate discriminative power (AUC = 0.81) for pediatric inactive IBD, but was not able to discriminate active or inactive adult IBD patients from controls. The AUC-ROC values did not confirm an ability of the mRNAs abundances to discriminate between active UC and active CD in pediatric or adult populations.Conclusions. This study identifies and validates blood transcriptional biomarkers that could be used in clinical settings as diagnostic predictors of IBD clinical activity in pediatric, but not adult, IBD patients.
Background and Aims. The study investigates the practical utility of whole blood gene expression profiling to diagnose inflammatory bowel diseases (IBDs).Methods. The discovery cohorts included 102 and 51 pediatric IBD patients and controls, and 95 and 46 adult IBD patients and controls, respectively. The replication cohorts included 447 and 76 pediatric IBD patients and controls, and 271 and 108 adult IBD patients and controls, respectively. In the discovery phase, RNA samples extracted from whole peripheral blood were analyzed using RNA-Seq and the predictive values of selected biomarkers were validated using quantitative (q)PCR.Results. 15 differentially expressed transcripts (adjusted P = 0.05) were selected from the discovery sequencing datasets. The Receiver Operating Characteristic curves and area under the curve (ROC-AUC) in replication analyses showed high discriminative power (AUC range, 0.91–0.98) for eleven mRNAs in pediatric patients with active IBD. By contrast, the AUC-ROC values ranged from 0.63 to 0.75 in comparison of inactive pediatric IBDs and active/inactive adult IBDs, indicating a lack of discriminative power. The best multi-mRNA diagnostic classifier showed moderate discriminative power (AUC = 0.81) for pediatric inactive IBD, but was not able to discriminate active or inactive adult IBD patients from controls. The AUC-ROC values did not confirm an ability of the mRNAs abundances to discriminate between active UC and active CD in pediatric or adult populations.Conclusions. This study identifies and validates blood transcriptional biomarkers that could be used in clinical settings as diagnostic predictors of IBD clinical activity in pediatric, but not adult, IBD patients.