Rxivist logo

Discovery of a simple two-gene expression biomarker in whole blood predictive of the need for treatment escalation in inflammatory bowel disease

By Jan K Nowak, Rahul Kalla, Alex T Adams, IBD Character Consortium, Jonas Halfvarson, Jack Satsangi

Posted 10 Jul 2021
medRxiv DOI: 10.1101/2021.07.09.21259804

Background and aims: The IBD-Character consortium has recruited large internationally based inception cohorts of treatment-naive inflammatory bowel disease (IBD) patients, providing a unique resource to derive a simple transcriptome signature in the field of prognostication. Methods: The discovery cohort (n=160) was recruited in Norway, Sweden and Spain. The replication inception cohort from the United Kingdom (n=97) was followed-up for a mean (SD) of 350 (228) days. Treatment escalation was formally defined as the need for a biologic agent, ciclosporin and/or surgery, instituted for disease flare after initial remission, or colectomy during the index admission for ulcerative colitis. Whole blood RNA was subject to paired-end sequencing. In the discovery cohort a simple procedure was applied, which exploited differences of transcript ratios. The ten top performing ratios were tested using Cox regression models in the validation cohort. Results: Newly diagnosed IBD patients with high CACNA1E/LRRC42 expression ratio had an increased risk of treatment intensification (validation cohort: HR=19.3, 95%CI 2.6-143.9, p=0.000005; AUC 0.76, 95%CI 0.66-0.86). In 51 patients with CRP < 3.5 mg/L, CACNA1E/LRRC42 still predicted escalation (HR=10.4; 95%CI 1.2-86.5, p=0.007). The second best performing transcript ratio was CACNA1E/CEACAM21 yielding a HR of 10.9 (95%CI 2.5-46.7, p=0.00002) and an AUC of 0.76 (95%CI 0.65-0.86) in the validation cohort. Conclusion: Transcriptomic profiling of an IBD inception cohort identified gene expression ratios CACNA1E/LRRC42 and CACNA1E/CEACAM21 as prognostic biomarkers. These were validated in a replication cohort as strongly associated with short- and long-term risk of treatment intensification and may provide valuable information in clinical decision-making.

Download data

  • Downloaded 211 times
  • Download rankings, all-time:
    • Site-wide: 145,361
    • In gastroenterology: 237
  • Year to date:
    • Site-wide: 43,543
  • Since beginning of last month:
    • Site-wide: 45,298

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide