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

Abstract

Abstract. 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.

Gene expression and pathway analysis of CTNNB1 in cancer and stem cells

“…It has been reported that cadherin 1 ( CDH1 ) is up-regulated in diffuse-type GC cells compared to MSCs[9]. However, CDH2 was down-regulated in diffuse-type GC cells compared to MSCs; this provides a useful indicator - the ratio of CDH2 to CDH1 expression - to distinguish the mesenchymal and epithelial phenotypes of the cells[9]. It has been reported that catenin β 1 ( CTNNB1 ) is mutated in hepatocellular carcinoma[10,11].…”

Network pharmacology dissection of multiscale mechanisms of herbal medicines in stage IV gastric adenocarcinoma treatment

“…The metastatic process included tumor cell detachment, local invasion, motility, angiogenesis, vessel invasion, survival in the circulation, adhesion to endothelial cells, extravasation, and regrowth in different organs. [30,31] Interestingly, 25.5% of these genes were primarily involved in cell adhesion, cell migration, extracellular matrix disassembly, blood vessel development, and wound healing associated with gastric adenocarcinoma metastases, such as collagen families, [20,23,32,33] fibronectin 1, [20,23,34] and matrix metalloproteinases (MMPs) families. [20,23,35–39] Some cell proliferation-related genes, such as MYC, [20,23,40] cyclin E1, [20,23,41] CDC28 protein kinase regulatory subunit 1, [20,42,43] CDC28 protein kinase regulatory subunit 2, [23,43] cyclin-dependent kinase 4, [20,23,44] and proliferating cell nuclear antigen, [20,44,45] EGFR, [20,44,46] FGFR4, [20,23] insulin like growth factor 2, [20] cell division cycle 25B, [47] human epidermal growth factor receptor 2, [44,45] and protein kinase, DNA-activated, catalytic polypeptide, [48] have been previously reported as showing extremely high levels of expression in gastric adenocarcinoma.…”

MIR210 as a potential molecular target to block invasion and metastasis of gastric cancer

“…The epithelial-mesenchymal transition (EMT) is a process by which epithelial cells lose their cell polarity and normal cell-cell contacts, and become migratory, invasive, and mesenchymal stem cell-like [6]. Normal mesenchymal stem cells are multipotent stromal cells that can differentiate into a variety of cell types so that EMT has a role in tissue regeneration, such as in response to wounding.…”