In Pursuit of a Clinically Useful Biomarker for Abdominal Pain, is mRNA the Answer?
Tristan Jordan
A useful biomarker is a measurable substance whose presence can improve risk stratification, minimize the use of unnecessary procedures, and more quickly direct the patient to appropriate management. The most effective biomarkers, such as troponin for myocardial infarction, are routinely incorporated into the standard work-ups of patients with undifferentiated chest pain in the ED. Unfortunately, there is no troponin equivalent for patients who present to the ED with potentially serious causes of abdominal pain such as appendicitis or intra-abdominal abscess.
Messenger RNA (mRNA) represents a novel class of biomarkers. Specific diseases may be associated with a detectable mRNA fingerprint that could improve our diagnostic capabilities. A growing sector of diagnostics already utilizes RNA to produce actionable clinical information. For instance, Oncotype Dx is an FDA-approved test used to evaluate the risk of recurrence in patients with a particular type of early-stage breast cancer1. Differential RNA expression is also associated with the activation of circulating neutrophils2. Likely, the RNAs code for proteins that have important functions in innate immunity and are associated with host responses to bacterial biofilms, which are involved in the pathogenesis of diseases such as acute appendicitis. By examining specific changes in these mRNA biomarkers, we may improve clinical decision-making and rule-out or rule-in the presence of an internal infection.
Studies are ongoing at George Washington University to evaluate the clinical utility of mRNA biomarker to diagnose acute appendicitis and other intra-abdominal infections. The application of this technology to address gaps in diagnostics is an exciting development in medicine. According to Genetics professor Dr. Tim McCaffrey, “RNA-based diagnostics represent a largely untapped resource for diagnostics that are extremely flexible and can be quantified very precisely. We see opportunities for improved physician guidance in almost every medical specialty.” Emergency Medicine professor Dr. Andrew Meltzer adds that “Abdominal pain is the most common presenting complaint in the ED and RNA research is focused on improving diagnostic testing modalities to provide early risk stratification and diagnosis.”
___________________________________________________________________
References
1. Kwa M, Makris A, Esteva FJ. Clinical utility of gene-expression signatures in early stage breast cancer. Nat Rev Clin Oncol. 2017;14(10):595–610. doi: 10.1038/nrclinonc.2017.74 [doi].
2. Chawla LS, Toma I, Davison D, et al. Acute appendicitis: Transcript profiling of blood identifies promising biomarkers and potential underlying processes. BMC Med Genomics. 2016;9(1):40-y. doi: 10.1186/s12920–016–0200-y [doi].
___________________________________________________________________
Tristan Jordan is a second year medical student at The George Washington University School of Medicine and Health Sciences with an interest in translational medicine and global health. He has previously worked as a research fellow at the National Institute of Allergy and Infectious Diseases.
