Cell of origin and expression profiles of pseudomyxoma peritonei derived from the appendix

Pseudomyxoma peritonei (PMP) is a rare disease caused by mucin-producing tumors developed most frequently from the appendix. This disease shows distinct clinical features by the cancerous cells producing mucin in the abdominal cavity. Although frequent mutations in the KRAS and GNAS genes have been reported in PMP, gene expression profiles of the tumors remain to be fully clarified because of its rarity and the difficulties in collecting pure cancerous cells scattered with a large volume of mucins. To disclose the molecular features of PMP cells, we performed RNA-seq analysis of ten PMPs and their matched non-tumorous colonic epithelium in combination with laser-microdissection. As a result, we identified a total of 5,747 differently expressed genes (DEGs) between the tumors and non-tumorous colonic epithelium. A cell-of-origin subtype analysis with nearest template prediction algorithm corroborated that PMP tumor cells belonged to the goblet cell subtype, suggesting that tumorous cells of PMP have a feature of differentiation to goblet cells. Interestingly, gene set enrichment analysis (GSEA) uncovered that the tumors were significantly associated with three ontology terms, namely epithelial mesenchymal transition (EMT), tumor necrosis factor-alpha (TNF-α), and angiogenesis. Comparison of gene expression profiles between disseminated peritoneal adenomucinosis (DPAM) and peritoneal mucinous adenocarcinomas (PMCA) identified a total of 687 DEGs. Additional GSEA revealed that ontology terms “G2M checkpoint” and “E2F targets” were significantly enriched in PMCA supporting the view that PMCA has more aggressive properties than DPAM. These data may be useful for the understanding of molecular characteristics of PMP.