Mapping intestinal metaplasia progression across the upper gastrointestinal tract through a common precancer lens

Intestinal metaplasia is a precancerous condition that occurs in the oesophagus (known as Barrett's oesophagus, BO) and stomach (known as gastric intestinal metaplasia, GIM), which are precursors for oesophageal adenocarcinoma (OAC) and gastric cancer (GC), respectively.

Despite advancement in early detection, initiation and progression of these cancers remains poorly understood, hindering effective early detection strategies.

Our recent studies pointed to that BO and GIM may share common origin and developmental pathway, leading to several intriguing questions: a) Is there a common stem/progenitor cell population in BO and GIM? b) Are BO and GIM driven by distinct tissue microenvironment in different anatomic sites? c) How do these intrinsic and extrinsic features drive malignant progression in BO and GIM?

Addressing these queries could unravel mechanisms of BO/OAC and GIM/GC initiation and progression, aligning risk prediction strategies of precancerous development and malignant progression across the upper gastrointestinal tract.

Our research plans are: 1) Compare normal gastric stem cells at different sites to evaluate the cancer susceptibility and underlying mechanism of precancerous development. 2) Establish a biobank of patient-matched organoid trios from BO/OAC and GIM/GC, to map BO and GIM lineage-relatedness and routes of progression from normal tissue to (pre)malignancy. 3) Interrogate the tissue microenvironment of BO and GIM using spatial multiplex imaging technologies to understand how this contributes to disease initiation and progression.

Our work aims to unify early detection strategies for individuals at increased risk of upper gastrointestinal cancer, providing a roadmap for proactive interception and prevention.