Extracellular miRNAs for the Management of Barrett’s Esophagus and Esophageal Adenocarcinoma: A Systematic Review

Abstract

Esophageal adenocarcinoma (EAC), the major histologic type of esophageal cancer (EC) in Western countries, is a disease with a poor prognosis, primarily due to usual diagnosis at an advanced stage. The prevalence of EAC has increased in recent years, both in Western countries and in Asia. Barrett’s esophagus (BE) is a precursor lesion of EAC. Therefore, early detection and proper management of BE and EAC is important to improve prognosis. Here, we systematically summarize current knowledge about the potential utility of extracellular microRNAs (miRNAs), which are thought to be non-invasive biomarkers for many diseases, for these purposes. A search of the PubMed and Embase databases identified 22 papers about extracellular miRNAs that have potential utility for management of EAC. Among them, 19 were EAC-related and ten were BE-related; some of these dealt with both conditions. The articles included studies reporting diagnosis, prognosis, and treatment responses. Multiple papers report dysregulation of miR-194-5p in BE and miR-21-5p, -25-3p, and -93-5p in EAC. Although it will take time to utilize these miRNAs in clinical practice, they are likely to be useful non-invasive markers in the future.

Computational pathology aids derivation of microRNA biomarker signals from Cytosponge samples

“…Together with miR-25–3p, 45 they are upregulated in liquid biopsies of EAC patients compared to healthy individuals. 49 miR-31 is thought to be a progression marker via Wnt signalling, as it directly targets the Wnt inhibitor Dickkopf-related protein 1. 47 Another well-described oncogenic miR is miR-181b-5p, which has been shown to play a role in oesophageal squamous cell carcinoma (ESCC), 50 non-small cell lung cancer, 51 triple-negative breast cancer 52 and acute myeloid leukaemia 53 among others.…”

Epigenetic Alterations from Barrett’s Esophagus to Esophageal Adenocarcinoma

“…Additionally, the decreased expression of miR-215 in EAC suggests that it may have tumor suppressor properties. miR-203 plays a crucial role as a tumor suppressor in various types of cancer [110]. The ability to bind the 3 UTR of mRNA of jun proto-oncogene (c-Jun), which is a transcription factor involved in regulating cellular growth and differentiation, has potential in cancer treatment strategies.…”

Barrett's esophagus: The pathomorphological and molecular genetic keystones of neoplastic progression

“…231 Value of miRNAs in diagnostics is obvious (Table 7), besides levels of specific miRNAs may serve as prognostic markers and are also applicable for assessment of treatment efficacy and as therapeutic targets. [232][233][234] Epigenetic changes are the earliest in pathogenesis of BE, anticipating any genetic or molecular alterations during Barrett's carcinogenesis. Several epigenetic changes serve as stage-specific markers of neoplastic transformation which is important for precise diagnosis.…”

“…Value of miRNAs in diagnostics is obvious (Table 7 ), besides levels of specific miRNAs may serve as prognostic markers and are also applicable for assessment of treatment efficacy and as therapeutic targets. 232 , 233 , 234 …”