Zeitschrift für mukosale Immunologieforschung

Abstrakt

Highlights of Whole Genome Expression Array Profiling Esophageal adenocarcinoma and Barrett's oesophagus have different mucosal defence genes

Drake J Nacarow

Esophageal adenocarcinoma (EAC) has grown significantly in prevalence while having extremely low survival rates in Western nations. Barrett’s oesophagus (BE), which is thought to form as a outcome of recurrent gastro-esophageal reflux, is one of the major risk factors for the development of this cancer. In this study, we compared genome-wide expression profiles on total RNA isolated from esophageal biopsy tissues from individuals with EAC, BE (in the absence of EAC), and those with normal squamous epithelium. We used Illumina whole-genome Beadarrays for this. To analyse significant gene and ontology discrepancies between these three tissue states, we integrated these data with publicly available raw data from three related investigations. The findings are consistent with the hypothesis that BE is a tissue with improved glycoprotein synthesis machinery (DPP4, ATP2A3, and AGR2) created to provide robust mucosal defences to fend off gastro-esophageal reflux. EAC shows indications of decreased expression of genes linked to mucosal (MUC6, CA2, TFF1) and xenobiotic (AKR1C2, AKR1B10) defences, in addition to the accelerated extracellular matrix remodelling (collagens, IGFBP7, PLAU) impacts expected in an aggressive form of cancer. Keratin, mucin, annexin, and trefoil factor gene groups are the most commonly represented differentially expressed gene families when our data are compared to earlier whole-genome expression profiling research. At least three prior profiling studies have included at least one of the eleven genes we discovered here. We employed a support vector machine left one out cross validation (LOOCV) analysis to separate squamous epithelium, BE, and EAC within the two biggest cohorts. Although this approach was effective at differentiating between squamous epithelium and BE, it highlights the necessity for more thorough research on the differences in BE and EAC’s profile.