Comparative transcriptomic analyses reveal activation of the epithelial-mesenchymal transition program in non-metastasizing low grade pseudomyxoma peritonei

• DOI: 10.1016/j.prp.2024.155129
• Publication Date: 2024-01-16T18:52:33Z
• Authors: Elise Pretzsch; Jens Neumann; Hanno Nieß; Charlotte M. Pret...; F.O. Hofmann; Thomas Kirchner; Frederick Klauschen; Jens Werner; Martin Angele; Jörg Kumbrink
• Keywords: Pseudomyxoma Peritonei; MMP1

Epithelial-mesenchymal transition (EMT), angiogenesis, cell adhesion and extracellular matrix (ECM) interaction are essential for colorectal cancer (CRC) metastasis. Low grade mucinous neoplasia of the appendix (LAMN) its advanced state low pseudomyxoma peritonei (lgPMP) show local aggressiveness with very limited metastatic potential as opposed to CRC. To better understand underlying processes that foster or impede spread, we compared LAMN, lgPMP, CRC respect their molecular profile subsequent pathway analysis. lgPMP (mucinous) cases were subjected transcriptomic analysis utilizing Poly(A) RNA sequencing. Successfully sequenced (LAMN n = 10, 77%, 13, 100% 8, 100%) investigated using bioinformatic statistical tests (differential expression analysis, hierarchical clustering, principal component gene set enrichment analysis). We identified a signature 28 genes distinguishing neoplasias. Ontology analyses revealed multiple pathways including EMT, ECM angiogenesis differentially regulated. Fifty-three significantly regulated sets between followed by vs. LAMN (n 21) 16). Unexpectedly, substantial EMT was observed in (FDR=0.011) (FDR=0.004). Typical markers upregulated (Vimentin, TWIST1, N-Cadherin) downregulated (E-Cadherin) lgPMP. However, MMP1 MMP3 levels, associated metastasis, considerably higher different tumor biological behaviour spread pattern midgut malignancies is reflected profile. strong activation program non-metastasizing Hence, although considered key step hematogenous successful does not necessarily lead dissemination. This emphasizes need further forms basis mechanistic therapy-targeting research.