Single-Cell Transcriptomic Analysis of Tumor Heterogeneity and the Microenvironment in Pseudomyxoma Peritonei

Area of Science:

• Oncology
• Cancer Biology
• Genomics

Background:

• Pseudomyxoma peritonei (PMP) is a rare malignancy characterized by mucus accumulation, fibrosis, and frequent recurrence.
• The tumor microenvironment (TME) of PMP, especially in metastatic sites, is not well understood.
• Limited therapeutic options exist for PMP, necessitating research into novel treatment strategies.

Purpose of the Study:

• To construct a high-resolution atlas of primary and metastatic PMP tumors using multi-omics approaches.
• To elucidate the cellular composition and functional states within the PMP microenvironment.
• To identify potential therapeutic targets and pathways for PMP treatment.

Main Methods:

• Integrated single-cell RNA sequencing (scRNA-seq), whole-exome sequencing (WES), and bulk RNA sequencing.
• Histopathologic validation of identified cell populations and TME features.
• Retrospective analysis of recurrent PMP cases for therapeutic insights.

Main Results:

• Identified distinct epithelial cell states (TFF3+, MACC1+) in PMP.
• Revealed coordinated microenvironmental reprogramming in metastases, including fibrosis (POSTN+ fibroblasts), immunosuppression (CXCL5+ macrophages), and immune exclusion.
• Discovered a pro-angiogenic network (POSTN+, RSPO3+, endothelial cells) potentially mediated by VEGFA-VEGFR2 signaling.
• Observed extensive lipid metabolic activity within the TME.

Conclusions:

• This study provides a comprehensive single-cell transcriptomic atlas of PMP.
• The findings reveal key TME components and pathways driving PMP progression and metastasis.
• VEGFR2-targeted anti-angiogenic therapy shows potential for recurrent PMP, warranting further investigation.