Gene expression profile of tumors from the upper digestive track: from tumor biology to new diagnostic tools

Abstract

Tumors of the upper digestive track (stomach and esophagus) represent a major challenge in cancer research. The vast majority of tumors are presented at late stage, with extremely poor prognosis. Whereas stomach cancer is the second cause of cancer-related death world-wide, adenocarcinomas of the esophagus are leading the statistics of new cases in USA and Europe. Adenocarcinomas of both stomach and esophagus are associated with chronic inflammatory response leading to tissue remodeling and intestinal metaplasia, which is consider as a pathology with high risk of malignant transformation. Using cDNA microarrays, we determined the expression profile of samples representing normal and diseased mucosas of stomach and esophagus and, using mathematical and statistical tools, we identify molecular classifiers that might be important form early detection of malignant transformation. We also identify a series of genes belonging to functional modules related to cytokine responses and glicerolipid pathway as new candidates for causative effect in increased DNA damage. In this project, we aim to build a collaborative network of institutions and investigators in order to create a large sample bank with associated clinical data in order to validate previously obtained data as well as to further explore expression profile as a tool to better understand the biology of intestinal metaplasia and the molecular events related to its malignant transformation. The major spin-off from this project is that each participating institution will develop it own sample bank and, at the same time, get expertise in the various methods for gene expression analysis, enabling them to pursue independent research projects. (AU)