Transcriptomic Changes and Biomarkers in Barrett's Metaplasia, Dysplasia and Cancer

Esophageal adenocarcinoma (EAC) poses a significant challenge due to its poor five-year survival rate and rapidly increasing incidence. Dysplasia in Barrett's esophagus (BE) poses the primary risk for EAC development, shaping clinical management decisions. However, the reliability of histopathological dysplasia diagnosis is questionable, as it exhibits poor inter-observer agreement, emphasizing the requirement for innovative biomarkers to enhance diagnostic precision.

In this study, researchers conducted transcriptome profiling across the entire range of BE-related neoplasia, involving 85 samples. The goal was to identify gene expression alterations across progressively worsening disease stages and pinpoint biomarkers that could augment histopathology for better detection of dysplasia and EAC in endoscopic biopsy samples.

Differential gene expression and pathway analyses uncovered that the most significant transcriptional changes occurred during the shift from normal squamous epithelium to non-dysplastic BE (NDBE), indicative of metaplastic transformation. Compared to NDBE, dysplasia exhibited heightened cellular growth and proliferation. Furthermore, EAC displayed augmented immune processes and oncogenic signaling pathways.

Employing machine learning techniques, the researchers identified a novel five-gene panel with potential for a future RNAseq-based diagnostic test (SLC11A1, IL36A, LUCAT1, MIR215, RNU6-954P). They also performed an initial validation of this signature in an additional 51 samples.

Additionally, the study identified several potential novel immunohistochemical markers that warrant further exploration, such as TREM1, CXCL5, OSM, and motilin. In summary, by mapping transcriptional changes throughout the entire disease spectrum, this research identifies several candidate biomarkers to improve current diagnostic methods for Barrett's dysplasia and EAC.