AUTHOR=Albano Francesco , Russi Sabino , Laurino Simona , Mazzone Pellegrino , Di Paola Giuseppina , Zoppoli Pietro , Amendola Elena , Balzamo Chiara , Bartolo Ottavia , Ciuffi Mario , Ignomirelli Orazio , Sgambato Alessandro , Galasso Rocco , De Felice Mario , Falco Geppino , Calice Giovanni TITLE=Representing ECM composition and EMT pathways in gastric cancer using a new metastatic gene signature JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=Volume 12 - 2024 YEAR=2024 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2024.1481818 DOI=10.3389/fcell.2024.1481818 ISSN=2296-634X ABSTRACT=Gastric cancer (GC) is an aggressive and heterogeneous malignancy in which cancer cells start to invade through the stomach (stage I) until they metastasize to distant organs (stage IV), becoming lethal. We compared the gene expression profiles of 719 GC patients in seven different public datasets and identified a gene signature (APOD, COL1A2, FSTL1, GEM, LUM, and SPARC) characterizing stage IV disease, which is related to extracellular matrix (ECM) organization and the epithelial-tomesenchymal transition (EMT). We recreated a simplified ECM in vitro via the gene signature. This model recapitulates the signaling of metastatic disease, influencing the microenvironment and promoting cell invasion, triggering EMT.Overall, we identified a gene signature able to group Stage I GC patients at higher risk that is useful for the management of Stage I patients. Furthermore, our experimental model could be useful for further dissecting the molecular signaling that underlies the metastatic spread of cancer cells.