Related Experiment Video
Updated: Jun 4, 2025
Culture and Imaging of Ex Vivo Organotypic Pseudomyxoma Peritonei Tumor Slices from Resected Human Tumor Specimens
Published on: December 9, 2022
Cell of origin and expression profiles of pseudomyxoma peritonei derived from the appendix
Rei Noguchi1, Kiyoshi Yamaguchi1, Hideaki Yano2
1Division of Clinical Genome Research, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Abstract:
Pseudomyxoma peritonei (PMP) is a rare disease caused by mucin-producing tumors that develop most frequently from the appendix. The disease is characterized by the accumulation of 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 within the mucin. 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 32 differently expressed genes (DEGs) between the tumors and non-tumorous colonic epithelium. A cell-of-origin subtype analysis with the nearest template prediction algorithm corroborated that PMP tumor cells belonged to the goblet cell subtype, and tumorous cells of PMP appear to arise from goblet cells. Interestingly, over representation analysis (ORA) uncovered that the tumors were significantly associated with three ontology terms, namely epithelial mesenchymal transition (EMT), angiogenesis, and inflammatory response. Comparison of gene expression profiles between disseminated peritoneal adenomucinosis (DPAM) and peritoneal mucinous adenocarcinomas (PMCA) identified a total of 687 DEGs. Additional gene set enrichment analysis (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 to further understand the molecular characteristics of PMP.
Insights
Pseudomyxoma peritonei (PMP) arises from goblet cells, with gene expression linked to epithelial mesenchymal transition, angiogenesis, and inflammation. Advanced peritoneal mucinous adenocarcinomas show enriched cell cycle pathways, indicating greater aggressiveness.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Pseudomyxoma peritonei (PMP) is a rare mucin-producing tumor disease, often originating in the appendix.
- KRAS and GNAS gene mutations are common in PMP, but comprehensive gene expression profiles are lacking due to rarity and sample purity challenges.
- Understanding PMP molecular features is crucial for diagnosis and treatment.
Purpose of the Study:
- To elucidate the molecular characteristics of PMP cells using RNA-sequencing.
- To identify differentially expressed genes (DEGs) between PMP tumors and normal colonic epithelium.
- To determine the cell-of-origin and associated biological pathways in PMP.
Main Methods:
- RNA-sequencing (RNA-seq) was performed on ten PMP samples and matched non-tumorous colonic epithelium.
- Laser-microdissection was used to isolate pure cancerous cells.
- Cell-of-origin subtype analysis and over-representation analysis (ORA) were conducted.
Main Results:
- 32 differentially expressed genes (DEGs) were identified between PMP tumors and normal colonic epithelium.
- PMP tumor cells were confirmed to originate from goblet cells.
- ORA revealed significant associations with epithelial mesenchymal transition (EMT), angiogenesis, and inflammatory response.
- Comparison between disseminated peritoneal adenomucinosis (DPAM) and peritoneal mucinous adenocarcinomas (PMCA) identified 687 DEGs.
- PMCA showed enrichment in 'G2M checkpoint' and 'E2F targets', suggesting higher aggressiveness.
Conclusions:
- PMP tumor cells originate from goblet cells, with gene expression profiles linked to EMT, angiogenesis, and inflammation.
- Gene expression differences between DPAM and PMCA highlight distinct molecular features, with PMCA exhibiting more aggressive characteristics.
- These findings provide valuable insights into the molecular landscape of PMP, potentially aiding future therapeutic strategies.
More Related Videos
00:08Murine Appendectomy Model of Chronic Colitis Associated Colorectal Cancer by Precise Localization of Caecal Patch
Published on: August 24, 2019
09:00Modeling the Early Steps of Ovarian Cancer Dissemination in an Organotypic Culture of the Human Peritoneal Cavity
Published on: December 31, 2015
