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=12 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=Introduction

Gastric cancer (GC) is an aggressive and heterogeneous malignancy marked by cellular and molecular diversity. In GC, cancer cells invade locally in the stomach at stage I and can progress to metastasis in distant organs by stage IV, where it often becomes fatal.

Methods

We analyzed gene expression profiles from 719 stage I and stage IV GC patients across seven public datasets, conducting functional enrichment analysis to identify a gene signature linked to disease progression. Additionally, we developed an in vitro model of a simplified extracellular matrix (ECM) for cell-based assays.

Results

Our analysis identified a progression-associated gene signature (APOD, COL1A2, FSTL1, GEM, LUM, and SPARC) that characterizes stage IV GC. This signature is associated with ECM organization and epithelial-to-mesenchymal transition (EMT), both of which influence the tumor microenvironment by promoting cell invasion and triggering EMT.

Discussion

This gene signature may help identify stage I GC patients at higher risk, offering potential utility in early-stage patient management. Furthermore, our experimental ECM model may serve as a platform for investigating molecular mechanisms underlying metastatic spread in gastric cancer.