Proteomic analysis of gastric cancero patient-derived tissue ECM

ABSTRACT: Gastric cancer (GC) is a highly heterogeneous disease regarding histologic features, genotypes, and molecular phenotypes. Here, we investigated extracellular matrix (ECM)-centric analysis, examining its association with histologic subtypes and patient prognosis in human gastric cancer. We performed quantitative proteomic analysis of decellularized GC tissues that uncovered tumorous ECM, highlighting intertumoral heterogeneity in ECM composition. We identified 20 tumor-enriched proteins including four glycoproteins, serpin family H Member 1 (SERPINH1), Annexin family (ANXA3/4/5/13), S100A family (S100A6/8/9), MMP14, and other matrisome-associated proteins. In addition to these overall tumor-specific ECM proteins, histopathological characteristics of GC revealed variations in ECM composition, with the poorly cohesive carcinoma not otherwise specified (PCC-NOS) subtype being distinctly demarcated from other histologic subtypes. Integrating ECM proteomics with single-cell RNA sequencing, we identified crucial molecular markers in the PCC-NOS-specific stroma. PCC-NOS-enriched matrisome proteins (PEMs) and gene expression signatures of adipogenic cancer-associated fibroblasts (CAFadi) were closely linked, both associated with adverse outcomes in GC. Using tumor microarray analysis, we confirmed the CAFadi surface marker, ATP binding cassette subfamily A member 8 (ABCA8), predominantly present in PCC-NOS tumors. Our ECM-focused approach in identifying stromal characteristics paves the way for studies to determine their utility as biomarkers for patient stratification, offering valuable insights for linking molecular and histologic features in GC.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Jin Young Kim  

PROVIDER: MSV000093859 | MassIVE | Fri Jan 12 23:19:00 GMT 2024

SECONDARY ACCESSION(S): PXD048518

REPOSITORIES: MassIVE