Gene expression signatures for identifying diffuse-type gastric cancer associated with epithelial-mesenchymal transition.

Epithelial-mesenchymal transition (EMT) is associated with tumor malignancy. The hedgehog-EMT pathway is preferentially activated in diffuse-type gastric cancer (GC) compared with intestinal-type GC; however, histological typing is currently the only method for distinguishing these two major types of GC. We compared the gene expression profiles of 12 bone marrow-derived mesenchymal stem cell cultures and 5 diffuse-type GC tissue samples. Numerous upregulated or downregulated genes were identified in diffuse-type GC, including CDH1, CDH2, VIM, WNT4 and WNT5. Among these genes, the mRNA ratio of CDH2 to CDH1 could distinguish the 15 diffuse-type GC samples from the 17 intestinal-type GC samples. Our results suggested that the mesenchymal features were more prominent in diffuse-type GC than in intestinal-type GC, but were weaker in diffuse-type GC than in mesenchymal stem cells. Diffuse-type GC that has undergone extensive EMT, which has a poor prognosis, can be identified by quantitative PCR analysis of only two genes.