The sequential process prior to the appearance of a gastric or esophageal adenocarcinoma is a sequential histologically well-defined process characterized by the appearance of an intestinal phenotype. In the first stages of gastro-esophageal carcinogenesis the expression of intestinal markers, as intestinal transcription factors (CDX2), mucin genes (MUC2 and MUC4), intestinal enzymes and others, can be detected.

We study the molecular mechanisms that can be initiating these processes, through the regulation of transcription factors inducing the acquisition of the intestinal phenotype. In the esophagus, the development of columnar metaplasia (Barrett’s esophagus) is a response to a chronic gastroesophageal reflux injury and is a major risk factor for esophageal adenocarcinoma.

Patients undergoing esophagectomy with a gastric conduit reconstruction develop columnar metaplasia in the remnant esophagus on a background of significant reflux, providing a useful model to study the early molecular events in the development of Barrett’s esophagus. MiRNAs expression profiles may identify a characteristic signature that could distinguish between normal squamous epithelium, esophagitis, cardiac-type epithelium, and intestinal metaplasia.

We have identified miR24-3p as a negative regulator of CDX2, a transcription factor involved in the development of Barrett’s esophagus, in samples of cardiac-type mucosa with different stages of intestinalization.

We are currently analysing the value of a metabolic signature identified by a metabolomics approach as a biomarker for the early detection, treatment optimization, and follow-up of patients with gastroesophageal cancer.