Integrated single-nuclear RNA sequencing analysis reveals distinct characteristics of mucinous adenocarcinoma in right-sided colon cancer.

Mucinous adenocarcinoma (MAC) is a unique histological subtype of colorectal cancer (CRC), which usually occurs in the right-sided colon with poor prognosis. Our previous studies reveled unique clinicopathological characteristic of MAC, but the distinct molecular features and tumor microenvironment (TME) characteristics remain clarify systematically. In this study, we conducted a single nuclear RNA sequencing (snRNA-seq) analysis for CRC tissues with different histological subtypes, including MAC, partial mucinous adenocarcinoma (pMAC) and non-specific adenocarcinoma (AC). Our results show that MAC has a unique transcriptome profile and a distinct single-cell characteristic. It exhibited a higher degree of tumor purity but a lower composition of TME. MAC had a distinct cell-cell communication microenvironment and a particular evolutionary trajectory. The EpithelialCells of MAC closely interacted with fibroblasts, endothelial cells, and mural cells clusters. Furthermore, molecular functional characteristics analysis revealed that MAC enriched EpithelialCells, Fibroblasts, and Endothelial cells clusters have a high active in glycolysis, inflammation, and angiogenesis respectively. This comprehensive study first demonstrated that MAC is a unique histological subtype of right-sided CRC in the single cell level, and elucidated its tumor microenvironment composition and biological function characteristics, which will help us better understand the intrinsic feature of MAC.